☆ 4.8 Review

Advanced Techniques for Detecting Protein Misfolding and Aggregation in Cellular Environments

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H-1-Detected Biomolecular NMR under Fast Magic-Angle Spinning

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Radio Signals from Live Cells: The Coming of Age of In-Cell Solution NMR

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In-Cell NMR Spectroscopy of Functional Riboswitch Aptamers in Eukaryotic Cells

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A General Strategy to Control Viscosity Sensitivity of Molecular Rotor-Based Fluorophores

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Cryo-electron tomography provides topological insights into mutant huntingtin exon 1 and polyQ aggregates

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Posttranslational Modifications Mediate the Structural Diversity of Tauopathy Strains

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Hierarchical chemical determination of amyloid polymorphs in neurodegenerative disease

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Summary: Amyloid aggregation disrupts protein homeostasis in neurodegenerative diseases. The structural diversity is crucial to amyloid pathology, with chemical modifications playing a key role in the formation of stable structures. Research aims to highlight the importance of these modifications in amyloid assembly and pathology.

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Characterizing proteins in a native bacterial environment using solid-state NMR spectroscopy

Siddarth Narasimhan et al.

Summary: Solid-state nuclear magnetic resonance (ssNMR) has been widely used to study complex biomolecular systems. This protocol outlines a biochemical preparation scheme for obtaining cellular samples of soluble and insoluble or membrane-associated proteins, suitable for studying a protein of interest in both whole cells and in cell envelope or isolated membrane preparations.

NATURE PROTOCOLS (2021)

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Article Multidisciplinary Sciences

Molecular structure of a prevalent amyloid-β fibril polymorph from Alzheimer's disease brain tissue

Ujjayini Ghosh et al.

Summary: The study revealed the molecular structure of a specific fibril polymorph of Aβ40, derived from cortical tissue of an AD patient, which has unique features and may contribute to the development of structure-specific amyloid imaging agents and aggregation inhibitors.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2021)

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Article Chemistry, Analytical

Advanced In Vivo Cross-Linking Mass Spectrometry Platform to Characterize Proteome-Wide Protein Interactions

Martial Rey et al.

Summary: The study developed an advanced in vivo cross-linking mass spectrometry platform for investigating cellular interactome of living bacterial cells. The approach successfully captured and characterized highly dynamic multiprotein complexes in all bacterial compartments, demonstrating the potential and precision of the proteome-wide approach.

ANALYTICAL CHEMISTRY (2021)

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Article Biochemical Research Methods

Analysis of Brain Protein Stability Changes in Mouse Models of Normal Aging and α-Synucleinopathy Reveals Age- and Disease-Related Differences

Renze Ma et al.

Summary: Using the SPROX technique, the study analyzed the thermodynamic stabilities of proteins in brain tissue cell lysates from Hu α-Syn(A53T) transgenic mice at different time points. It identified a group of proteins with age-related stability changes and a group with differential stability in the transgenic mouse model. Some of these proteins have been previously detected in human cerebral spinal fluid and could potentially serve as biomarkers for Parkinson's disease.

JOURNAL OF PROTEOME RESEARCH (2021)

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Article Biochemistry & Molecular Biology

Raman spectral imaging of 13C2H15N-labeled a-synuclein amyloid fibrils in cells

Matthew D. Watson et al.

Summary: The study utilized isotopically labeled α-synuclein to investigate the localization of preformed fibrils within cells, showcasing the power of Raman spectroscopy in providing secondary structural information and distinct protein differentiation through unique vibrational frequencies.

BIOPHYSICAL CHEMISTRY (2021)

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Article Chemistry, Multidisciplinary

In-Cell Sensitivity-Enhanced NMR of Intact Viable Mammalian Cells

Rupam Ghosh et al.

Summary: NMR combined with DNP enhances sensitivity and resolution for detecting proteins, but sensitivity gains are influenced by experimental conditions and sample composition, leading to uncertainty about cellular sample integrity.

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2021)

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Article Chemistry, Multidisciplinary

O-Glycosylation Induces Amyloid-β To Form New Fibril Polymorphs Vulnerable for Degradation

Dangliang Liu et al.

Summary: The study demonstrates that O-glycans significantly impact both the aggregation and degradation of Aβ(42). A Galβ1-3GalNAc modification redirects Aβ(42) to form a new fibril polymorphic structure, which is less stable and more vulnerable to Aβ-degrading enzymes such as the insulin-degrading enzyme.

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2021)

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Article Multidisciplinary Sciences

Whole-cell organelle segmentation in volume electron microscopy

Larissa Heinrich et al.

Summary: FIB-SEM combined with deep-learning-based segmentation is used to produce 3D reconstructions of cells with annotated organelle classes. The automatic reconstruction method enables detailed understanding of cellular organization and spatial interactions, with potential applications in correlative studies. An open data repository, 'OpenOrganelle', has been created to share data and models for further scientific exploration.

NATURE (2021)

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Article Multidisciplinary Sciences

Structure-based classification of tauopathies

Yang Shi et al.

Summary: The structures of tau filaments from different tauopathies vary, allowing for a hierarchical classification of these diseases. Some tauopathies share similar filament folds, while others have distinct folding patterns.

NATURE (2021)

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Article Multidisciplinary Sciences

Structural differences in amyloid-β fibrils from brains of nondemented elderly individuals and Alzheimer's disease patients

Ujjayini Ghosh et al.

Summary: This study investigated the molecular structures of Aβ fibrils in brain tissue of nondemented elderly individuals and AD patients using solid-state NMR, revealing that similar sets of fibril polymorphs develop in both groups but with different relative populations on average. The differences in solid-state NMR data were more significant for Aβ42 fibrils compared to Aβ40 fibrils.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2021)

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Article Chemistry, Analytical

A label-free fluorescent probe for dynamic in situ visualization of amyloid-beta peptides aggregation

Cen Ding et al.

Summary: A label-free fluorescent probe (BTS) was reported for dynamic in situ visualization of A beta 40 aggregation. The probe binds to all forms of A beta 40 with high affinity and can monitor the entire A beta aggregation process with high selectivity and sensitivity.

SENSORS AND ACTUATORS B-CHEMICAL (2021)

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Article Chemistry, Analytical

Amyloid-β oligomer targeted theranostic probes for in vivo NIR imaging and inhibition of self-aggregation and amyloid-β induced ROS generation

Xueli Wang et al.

Summary: Novel near infrared emissive fluorophores exhibit strong selectivity towards Aβ oligomers and monomers, good biocompatibility and stability, and significant inhibitory effects on Aβ aggregation.

TALANTA (2021)

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Article Multidisciplinary Sciences

Cryo-EM structure of amyloid fibrils formed by the entire low complexity domain of TDP-43

Qiuye Li et al.

Summary: The study presents the cryo-EM structure of amyloid formed from the complete C-terminal TDP-43 low complexity domain and discusses the potential structural perturbations caused by phosphorylation and disease-related mutations. The findings reveal differences in the structural features of these fibrils compared to those generated from short protein fragments, providing insight into the mechanisms underlying neurodegenerative diseases like ALS and FTLD.

NATURE COMMUNICATIONS (2021)

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Article Multidisciplinary Sciences

The hereditary mutation G51D unlocks a distinct fibril strain transmissible to wild-type α-synuclein

Yunpeng Sun et al.

Summary: The study demonstrates that the G51D mutation induces a distinct fibril strain of alpha-syn in vitro, with the corresponding structure determined by cryo-EM.

NATURE COMMUNICATIONS (2021)

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Article Multidisciplinary Sciences

Nuclear and cytoplasmic huntingtin inclusions exhibit distinct biochemical composition, interactome and ultrastructural properties

Nathan Riguet et al.

Summary: This study investigates the ultrastructural and biochemical properties of huntingtin cytoplasmic and nuclear inclusions, showing that they form via distinct mechanisms and exert their toxicity via different pathways. The findings provide insight into the complex processes of Htt inclusion formation and maturation, involving polyQ-dependent aggregation, sequestration of lipids and proteins related to HD pathways, accumulation of dysfunctional organelles, and impairment of protein quality control mechanisms. Nuclear and cytoplasmic Htt inclusions exhibit distinct compositions and properties, suggesting different mechanisms of aggregation and toxicity.

NATURE COMMUNICATIONS (2021)

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Article Engineering, Biomedical

Construction of a Highly Sensitive Thiol-Reactive AIEgen-Peptide Conjugate for Monitoring Protein Unfolding and Aggregation in Cells

Soheila Sabouri et al.

Summary: The impairment of protein quality control network leads to unfolded and aggregated proteins accumulation. A new platform based on an AIEgen is reported for labeling and tracking unfolded proteins in cells. The rational design demonstrates the potential of diverse functional groups for maximal sensitivity and selectivity in biological samples.

ADVANCED HEALTHCARE MATERIALS (2021)

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Article Biochemistry & Molecular Biology

Fluorescent Probe for Selective Imaging of a-Synuclein Fibrils in Living Cells

Pankaj Gaur et al.

Summary: In this study, two molecular rotor-based probes RB1 and RB2 are presented, with RB1 showing outstanding absorption red-shift and high fluorescence enhancement, exhibiting high affinity and selective staining ability for alpha-synuclein fibrils in living cells. RB1 can be used for intracellular imaging of alpha-synuclein fibrils due to its strong binding affinity and cell-permeable nature.

ACS CHEMICAL NEUROSCIENCE (2021)

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Article Clinical Neurology

Cryo-EM structures of tau filaments from Alzheimer's disease with PET ligand APN-1607

Yang Shi et al.

Summary: A newly described PET ligand, APN-1607, was found to bind to specific sites in the Alzheimer's disease fold, potentially leading to the development of new ligands with increased specificity and binding activity. Additionally, tau filaments from posterior cortical atrophy (PCA) and primary age-related tauopathy (PART) were shown to be identical to those from AD.

ACTA NEUROPATHOLOGICA (2021)

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Article Chemistry, Multidisciplinary

Rational Design of Crystallization-Induced-Emission Probes To Detect Amorphous Protein Aggregation in Live Cells

Di Shen et al.

Summary: This study developed sensors for amorphous protein aggregation from aggregation-induced-emission probes (AIEgens) with controllable sensitivity, spectral coverage, and cellular performance through rational design.

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION (2021)

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Article Chemistry, Multidisciplinary

Local Deuteration Enables NMR Observation of Methyl Groups in Proteins from Eukaryotic and Cell-Free Expression Systems

Abhinav Dubey et al.

Summary: Methyl-group NMR spectroscopy is beneficial for structural studies of complex biological systems, but labeling requirements have hindered its use in new protein expression systems. Researchers have developed a five-step synthesis method for stereo-selective methyl-labeled leucine, enabling applications in eucaryotic or cell-free expression systems and providing NMR sensors for previously inaccessible protein systems.

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION (2021)

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Article Biochemical Research Methods

Enabling Photoactivated Cross-Linking Mass Spectrometric Analysis of Protein Complexes by Novel MS-Cleavable Cross-Linkers

Craig Gutierrez et al.

Summary: XL-MS is a powerful tool for studying protein-protein interactions and elucidating architectures of protein complexes. The development of novel MS-cleavable heterobifunctional cross-linkers, such as SDASO, enables fast and accurate identification of photocross-linked peptides by MSn. The feasibility of photocross-linking large protein complexes has been demonstrated, laying the foundation for future applications in complex XL-MS studies.

MOLECULAR & CELLULAR PROTEOMICS (2021)

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Article Multidisciplinary Sciences

The structure of a minimum amyloid fibril core formed by necroptosis-mediating RHIM of human RIPK3

Xialian Wu et al.

Summary: RIPK3, a key protein involved in necroptosis, forms amyloid fibrils via its RHIM domain. The study determined the fibril structure of RIPK3 C-terminal domain containing RHIM using cryo-EM and solid-state NMR. The unique assembly of RIPK3-CTD fibril may contribute to efficient phosphorylation of RIPK3 kinase domain.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2021)

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Article Multidisciplinary Sciences

Wild-type α-synuclein inherits the structure and exacerbated neuropathology of E46K mutant fibril strain by cross-seeding

Houfang Long et al.

Summary: Our research has shown that WT mice inoculated with the human E46K mutant alpha-syn fibril (hE46K) strain exhibit early-onset motor deficits and morphologically different alpha-syn aggregation compared to those inoculated with the human WT fibril (hWT) strain. Cryoelectron microscopy has revealed that the hE46K strain induces both human and mouse WT alpha-syn monomers to form the fibril structure of the hE46K strain at the near-atomic level. Furthermore, the induced hWT strain inherits most of the pathological traits of the hE46K strain, suggesting that mutant strains' structural and pathological features could be propagated by the WT alpha-syn and amplified in familial Parkinson's diseases.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2021)

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Article Multidisciplinary Sciences

In situ architecture of neuronal α-Synuclein inclusions

Victoria A. Trinkaus et al.

Summary: The study used cryo-electron tomography to show that neuronal alpha-Syn inclusions consist of a mixture of fibrils and cellular organelles, without direct interaction between the fibrils and membranes.

NATURE COMMUNICATIONS (2021)

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Article Biology

Multimodal, label-free fluorescence and Raman imaging of amyloid deposits in snap-frozen Alzheimer's disease human brain tissue

Benjamin Lochocki et al.

Summary: The study conducted comprehensive investigation of amyloid deposits in frozen AD human brain tissue utilizing high-resolution fluorescence and spectroscopic imaging techniques. Variations in plaque types were observed, with Raman spectroscopy indicating changes in protein structure in cored amyloid deposits. Carotenoids were identified as a potential marker for distinguishing plaque areas from non-plaque areas without prior knowledge of their location.

COMMUNICATIONS BIOLOGY (2021)

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Article Biochemistry & Molecular Biology

Live-cell ATR-FTIR spectroscopy as a novel bioanalytical tool for cell glucose metabolism research

Anchisa Poonprasartporn et al.

Summary: FTIR spectroscopy is a nondestructive, label-free and low-cost technique that can be used to study metabolic changes in cells. The study demonstrated that live-cell FTIR can effectively highlight differences in glucose metabolism in cells treated with normal and high glucose medium, showing significant differences in spectra.

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH (2021)

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Review Biochemistry & Molecular Biology

Towards Visual Proteomics at High Resolution

Felix J. B. Baeuerlein et al.

Summary: Traditionally, structural biologists have approached the complexity of cellular proteomes in a reductionist manner, but a new method called visual proteomics aims to obtain a holistic picture of cellular proteomes by studying them in situ. Cryo-electron tomography is the highest resolution method currently available for this purpose, allowing visualization of cellular landscapes with molecular resolution and revealing interaction networks underlying cellular functions.

JOURNAL OF MOLECULAR BIOLOGY (2021)

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Article Chemistry, Multidisciplinary

Sensitivity-Enhanced Solid-State NMR Detection of Structural Differences and Unique Polymorphs in Pico- to Nanomolar Amounts of Brain-Derived and Synthetic 42-Residue Amyloid-β Fibrils

Ayesha Wickramasinghe et al.

Summary: The Aβ-plaques are a hallmark of Alzheimer's disease, and structural characterization of Aβ fibrils, especially Aβ42, is crucial for understanding AD pathogenesis. Sensitivity-enhanced H-1-detected solid-state NMR is demonstrated to be feasible for characterizing the structure of trace amounts of brain-derived and synthetic amyloid fibrils. This technique allows for rapid detection of structural differences between AD-derived Aβ42 fibrils and synthetic fibrils, indicating its potential for assessing amyloid fibril structure.

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2021)

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Article Chemistry, Multidisciplinary

Nonrefoldability is Pervasive Across the E. coli Proteome

Philip To et al.

Summary: The study reveals that one-third of the E. coli proteome is not intrinsically refoldable on physiological time scales, and this cohort is enriched with certain fold-types and domain organizations.

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2021)

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Article Spectroscopy

Potential of Raman spectroscopic techniques to study proteins

Nikki Kuhar et al.

Summary: Proteins, responsible for various biological processes, must maintain correct folding to avoid diseases. Raman spectroscopy techniques, including ROA, provide insights into protein structure and conformational changes, helping differentiate between proteins and understand subtle changes in their conformation. Techniques and data analyses advancements in Raman spectroscopic studies of proteins continue to be explored for a deeper understanding of protein structures.

SPECTROCHIMICA ACTA PART A-MOLECULAR AND BIOMOLECULAR SPECTROSCOPY (2021)

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Article Chemistry, Multidisciplinary

Turn-On Quinoline-Based Fluorescent Probe for Selective Imaging of Tau Aggregates in Alzheimer's Disease: Rational Design, Synthesis, and Molecular Docking

Ahmed A. Elbatrawy et al.

Summary: The newly designed quinoline fluorescent probe, Qtau 4, shows selective imaging of tau aggregates with favorable photophysical properties and high binding affinity, exhibiting 3.5-fold selectivity towards tau fibrils and successfully used for fluorescence imaging of human AD brain tissues.

ACS SENSORS (2021)

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Article Multidisciplinary Sciences

Genetic prion disease-related mutation E196K displays a novel amyloid fibril structure revealed by cryo-EM

Li-Qiang Wang et al.

Summary: This study revealed the structure of amyloid fibrils formed by full-length human PrP with E196K mutation, which differs from wild-type PrP and hamster brain-derived prion fibrils. The results highlight the importance of familial mutations in inducing different prion strains.

SCIENCE ADVANCES (2021)

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Article Chemistry, Analytical

High spatial-resolution imaging of label-free in vivo protein aggregates by VISTA

Li-En Lin et al.

Summary: Amyloid aggregation, a pathological hallmark in neurodegenerative diseases, was studied using label-free high-resolution imaging and machine learning for specific segmentation of aggregate cores and peripheral filaments. This non-invasive imaging technology allows precise and multiplex high-resolution imaging of protein aggregates and their micro-environment, opening up new biomedical applications.

ANALYST (2021)

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Review Multidisciplinary Sciences

Solid-state NMR spectroscopy

Bernd Reif et al.

Summary: Solid-state nuclear magnetic resonance (NMR) spectroscopy is an atomic-level method to determine the chemical structure, 3D structure, and dynamics of solids and semi-solids, with most high-resolution solid-state NMR spectra measured under magic-angle spinning (MAS). Common experiments and data analysis approaches in solid-state NMR are summarized, highlighting applications in biology, chemistry, and materials sciences.

NATURE REVIEWS METHODS PRIMERS (2021)

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Article Chemistry, Multidisciplinary

Amyloid-β Oligomer-Targeted Gadolinium-Based NIR/MR Dual-Modal Theranostic Nanoprobe for Alzheimer's Disease

Chengke Wang et al.

ADVANCED FUNCTIONAL MATERIALS (2020)

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Article Chemistry, Multidisciplinary

A Molecular Chameleon for Mapping Subcellular Polarity in an Unfolded Proteome Environment

Tze Cin Owyong et al.

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION (2020)

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Article Biochemistry & Molecular Biology

Structural Diversity of Amyloid Fibrils and Advances in Their Structure Determination

Dan Li et al.

BIOCHEMISTRY (2020)

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Article Biochemistry & Molecular Biology

High intracellular stability of the spidroin N-terminal domain in spite of abundant amyloidogenic segments revealed by in-cell hydrogen/deuterium exchange mass spectrometry

Margit Kaldmae et al.

FEBS JOURNAL (2020)

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Article Chemistry, Physical

Order, Disorder, and Reorder State of Lysozyme: Aggregation Mechanism by Raman Spectroscopy

Sandip Dolui et al.

JOURNAL OF PHYSICAL CHEMISTRY B (2020)

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Article Multidisciplinary Sciences

Novel tau filament fold in corticobasal degeneration

Wenjuan Zhang et al.

NATURE (2020)

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Article Multidisciplinary Sciences

Regulation of α-synuclein by chaperones in mammalian cells

Bjorn M. Burmann et al.

NATURE (2020)

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Article Biotechnology & Applied Microbiology

Identifying drug targets in tissues and whole blood with thermal-shift profiling

Jessica Perrin et al.

NATURE BIOTECHNOLOGY (2020)

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Article Multidisciplinary Sciences

Missing regions within the molecular architecture of human fibrin clots structurally resolved by XL-MS and integrative structural modeling

Oleg Klykov et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2020)

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Article Biochemistry & Molecular Biology

Validating Signal Transducer and Activator of Transcription (STAT) Protein-Inhibitor Interactions Using Biochemical and Cellular Thermal Shift Assays

Sanaz Attarha et al.

ACS CHEMICAL BIOLOGY (2020)

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Article Biochemistry & Molecular Biology

A Fluorogenic Molecule for Probing Islet Amyloid Using Flavonoid as a Scaffold Design

Wei-Ling Chen et al.

BIOCHEMISTRY (2020)

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Letter Cell Biology

Cryo-EM structure of full-length α-synuclein amyloid fibril with Parkinson's disease familial A53T mutation

Yunpeng Sun et al.

CELL RESEARCH (2020)

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Article Chemistry, Multidisciplinary

Live-Cell Imaging and Quantification of PolyQ Aggregates by Stimulated Raman Scattering of Selective Deuterium Labeling

Kun Miao et al.

ACS CENTRAL SCIENCE (2020)

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Article Multidisciplinary Sciences

Different regions of synaptic vesicle membrane regulate VAMP2 conformation for the SNARE assembly

Chuchu Wang et al.

NATURE COMMUNICATIONS (2020)

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Article Multidisciplinary Sciences

Parkinson's disease associated mutation E46K of α-synuclein triggers the formation of a distinct fibril structure

Kun Zhao et al.

NATURE COMMUNICATIONS (2020)

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Review Chemistry, Multidisciplinary

When Small becomes Too Big: Expanding the Use of In-Cell Solid-State NMR Spectroscopy

Siddarth Narasimhan et al.

CHEMPLUSCHEM (2020)

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Article Chemistry, Analytical

Fluorescent beta-ketoenole AmyGreen dye for visualization of amyloid components of bacterial biofilms

Olena Moshynets et al.

METHODS AND APPLICATIONS IN FLUORESCENCE (2020)

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Article Multidisciplinary Sciences

Structures of α-synuclein filaments from multiple system atrophy

Manuel Schweighauser et al.

NATURE (2020)

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Article Nanoscience & Nanotechnology

General Aggregation-Induced Emission Probes for Amyloid Inhibitors with Dual Inhibition Capacity against Amyloid β-Protein and α-Synuclein

Longgang Jia et al.

ACS APPLIED MATERIALS & INTERFACES (2020)

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Article Biochemistry & Molecular Biology

The In Situ Structure of Parkinson's Disease-Linked LRRK2

Reika Watanabe et al.

CELL (2020)

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Article Chemistry, Multidisciplinary

Environment-Sensitive Probes for Illuminating Amyloid Aggregation In Vitro and in Zebrafish

Francisco Fueyo-Gonzalez et al.

ACS SENSORS (2020)

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Article Biochemistry & Molecular Biology

Cryo-EM structure of an amyloid fibril formed by full-length human prion protein

Li-Qiang Wang et al.

NATURE STRUCTURAL & MOLECULAR BIOLOGY (2020)

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Article Multidisciplinary Sciences

Parkinson's disease-related phosphorylation at Tyr39 rearranges α-synuclein amyloid fibril structure revealed by cryo-EM

Kun Zhao et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2020)

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Review Biochemistry & Molecular Biology

The promise and the challenges of cryo-electron tomography

Martin Turk et al.

FEBS LETTERS (2020)

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Article Chemistry, Multidisciplinary

AggFluor: Fluorogenic Toolbox Enables Direct Visualization of the Multi-Step Protein Aggregation Process in Live Cells

Charles H. Wolstenholme et al.

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2020)

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Article Multidisciplinary Sciences

Single-particle cryo-EM at atomic resolution

Takanori Nakane et al.

NATURE (2020)

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Article Multidisciplinary Sciences

Atomic-resolution protein structure determination by cryo-EM

Ka Man Yip et al.

NATURE (2020)

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Review Cell Biology

Investigating the Structure of Neurotoxic Protein Aggregates Inside Cells

Felix J. B. Baeuerlein et al.

TRENDS IN CELL BIOLOGY (2020)

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Article Multidisciplinary Sciences

Topaz-Denoise: general deep denoising models for cryoEM and cryoET

Tristan Bepler et al.

NATURE COMMUNICATIONS (2020)

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Article Biochemistry & Molecular Biology

Polyphenol Honokiol and Flavone 2′,3′,4′-Trihydroxyflavone Differentially Interact with α-Synuclein at Distinct Phases of Aggregation

Blagojce Jovcevski et al.

ACS CHEMICAL NEUROSCIENCE (2020)

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Article Chemistry, Multidisciplinary

Synthesis and characterization of high affinity fluorogenic α-synuclein probes

Zsofia Lengyel-Zhand et al.

CHEMICAL COMMUNICATIONS (2020)

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Article Chemistry, Multidisciplinary

N,O-Benzamide difluoroboron complexes as near-infrared probes for the detection of β-amyloid and tau fibrils

Yimin Chen et al.

CHEMICAL COMMUNICATIONS (2020)

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Article Biochemistry & Molecular Biology

Studying assembly of the BAM complex in native membranes by cellular solid-state NMR spectroscopy

Cecilia Pinto et al.

JOURNAL OF STRUCTURAL BIOLOGY (2019)

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Review Biochemistry & Molecular Biology

Challenges and opportunities in cryo-EM single-particle analysis

Dmitry Lyumkis

JOURNAL OF BIOLOGICAL CHEMISTRY (2019)

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Article Biochemistry & Molecular Biology

Growth-driven displacement of protein aggregates along the cell length ensures partitioning to both daughter cells in Caulobacter crescentus

Frederic D. Schramm et al.

MOLECULAR MICROBIOLOGY (2019)

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Article Multidisciplinary Sciences

Novel tau filament fold in chronic traumatic encephalopathy encloses hydrophobic molecules

Benjamin Falcon et al.

NATURE (2019)

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Article Multidisciplinary Sciences

Fast pressure-jump all-atom simulations and experiments reveal site-specific protein dehydration-folding dynamics

Maxim B. Prigozhin et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2019)

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Article Multidisciplinary Sciences

Global analysis of methionine oxidation provides a census of folding stabilities for the human proteome

Ethan J. Walker et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2019)

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Article Biochemical Research Methods

Conformational ensemble of native -synuclein in solution as determined by short-distance crosslinking constraint-guided discrete molecular dynamics simulations

Nicholas I. Brodie et al.

PLOS COMPUTATIONAL BIOLOGY (2019)

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Article Biochemistry & Molecular Biology

Cadmium effects on superoxide dismutase 1 in human cells revealed by NMR

Panagis Polykretis et al.

REDOX BIOLOGY (2019)

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Article Chemistry, Multidisciplinary

High-Resolution Protein 3D Structure Determination in Living Eukaryotic Cells

Takashi Tanaka et al.

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION (2019)

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Review Biochemistry & Molecular Biology

Horizontal Cell Biology: Monitoring Global Changes of Protein Interaction States with the Proteome-Wide Cellular Thermal Shift Assay (CETSA)

Lingyun Dai et al.

ANNUAL REVIEW OF BIOCHEMISTRY, VOL 88 (2019)

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Article Biology

Heparin-induced tau filaments are polymorphic and differ from those in Alzheimer's and Pick's diseases

Wenjuan Zhang et al.

ELIFE (2019)

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Article Biochemistry & Molecular Biology

Advances in cryo-electron tomography and subtomogram averaging and classification

Peijun Zhang

CURRENT OPINION IN STRUCTURAL BIOLOGY (2019)

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Article Biochemistry & Molecular Biology

Structural Insights into α-Synuclein Fibril Polymorphism: Effects of Parkinson's Disease-Related C-Terminal Truncations

Xiaodan Ni et al.

JOURNAL OF MOLECULAR BIOLOGY (2019)

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Article Chemistry, Multidisciplinary

Characterization of Residue Specific Protein Folding and Unfolding Dynamics in Cells

Xiangfei Song et al.

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2019)

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Article Biochemical Research Methods

Metal Ion Binding to the Amyloid β Monomer Studied by Native Top-Down FTICR Mass Spectrometry

Frederik Lermyte et al.

JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY (2019)

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Article Biochemistry & Molecular Biology

Cryo-EM structures of four polymorphic TDP-43 amyloid cores

Qin Cao et al.

NATURE STRUCTURAL & MOLECULAR BIOLOGY (2019)

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Article Multidisciplinary Sciences

Tau local structure shields an amyloid-forming motif and controls aggregation propensity

Dailu Chen et al.

NATURE COMMUNICATIONS (2019)

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Article Multidisciplinary Sciences

Molecular mechanisms of heterogeneous oligomerization of huntingtin proteins

Silvia Bonfanti et al.

SCIENTIFIC REPORTS (2019)

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Article Chemistry, Multidisciplinary

Spontaneous Isomerization of Long-Lived Proteins Provides a Molecular Mechanism for the Lysosomal Failure Observed in Alzheimer's Disease

Tyler R. Lambeth et al.

ACS CENTRAL SCIENCE (2019)

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Article Biochemistry & Molecular Biology

Kinetic Transition in Amyloid Assembly as a Screening Assay for Oligomer-Selective Dyes

Jeremy Barton et al.

BIOMOLECULES (2019)

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Article Biochemistry & Molecular Biology

Toward high-resolution in situ structural biology with cryo-electron tomography and subtomogram averaging

Florian K. M. Schur

CURRENT OPINION IN STRUCTURAL BIOLOGY (2019)

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Article Multidisciplinary Sciences

Cryo-EM structure and polymorphism of Aβ amyloid fibrils purified from Alzheimer's brain tissue

Marius Kollmer et al.

NATURE COMMUNICATIONS (2019)

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Article Biochemistry & Molecular Biology

In-Cell NMR Study of Tau and MARK2 Phosphorylated Tau

Shengnan Zhang et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2019)

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Article Biochemistry & Molecular Biology

Live-cell super-resolution microscopy reveals a primary role for diffusion in polyglutamine-driven aggresome assembly

Meng Lu et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2019)

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Article Biochemistry & Molecular Biology

Structural progression of amyloid-β Arctic mutant aggregation in cells revealed by multiparametric imaging

Meng Lu et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2019)

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Article Chemistry, Multidisciplinary

Rational Design of Near-Infrared Aggregation-Induced-Emission Active Probes: In Situ Mapping of Annyloid-β Plaques with Ultrasensitivity and High-Fidelity

Wei Fu et al.

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2019)

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Review Biochemical Research Methods

In-Cell NMR Spectroscopy of Intrinsically Disordered Proteins

Nicholas Sciolino et al.

PROTEOMICS (2019)

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Article Chemistry, Multidisciplinary

Phosphorylation dependent α-synuclein degradation monitored by in-cell NMR

Wenwen Zheng et al.

CHEMICAL COMMUNICATIONS (2019)

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Article Biochemistry & Molecular Biology

Structural features of α-synuclein amyloid fibrils revealed by Raman spectroscopy

Jessica D. Flynn et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2018)

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Article Medicine, Research & Experimental

alpha-Synuclein: Multiple System Atrophy Prions

Amanda L. Woerman et al.

COLD SPRING HARBOR PERSPECTIVES IN MEDICINE (2018)

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In Situ Structural Characterization of a Recombinant Protein in Native Escherichia coli Membranes with Solid-State Magic-Angle-Spinning NMR

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JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2011)

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Fluorescence Ratiometry and Fluorescence Lifetime Imaging: Using a Single Molecular Sensor for Dual Mode Imaging of Cellular Viscosity

Xiaojun Peng et al.

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2011)

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In Situ Measurements of the Formation and Morphology of Intracellular β-Amyloid Fibrils by Super-Resolution Fluorescence Imaging

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JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2011)

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Development of a Novel Cross-linking Strategy for Fast and Accurate Identification of Cross-linked Peptides of Protein Complexes

Athit Kao et al.

MOLECULAR & CELLULAR PROTEOMICS (2011)

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α-Synuclein occurs physiologically as a helically folded tetramer that resists aggregation

Tim Bartels et al.

NATURE (2011)

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Molecular chaperones in protein folding and proteostasis

F. Ulrich Hartl et al.

NATURE (2011)

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Ligand binding to distinct states diverts aggregation of an amyloid-forming protein

Lucy A. Woods et al.

NATURE CHEMICAL BIOLOGY (2011)

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Ion mobility-mass spectrometry reveals a conformational conversion from random assembly to β-sheet in amyloid fibril formation

Christian Bleiholder et al.

NATURE CHEMISTRY (2011)

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Firefly luciferase mutants as sensors of proteome stress

Rajat Gupta et al.

NATURE METHODS (2011)

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Pyrroloquinoxaline hydrazones as fluorescent probes for amyloid fibrils

Sandra Gemma et al.

ORGANIC & BIOMOLECULAR CHEMISTRY (2011)

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In-cell NMR in E. coli to Monitor Maturation Steps of hSOD1

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PLOS ONE (2011)

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Structure and Intermolecular Dynamics of Aggregates Populated during Amyloid Fibril Formation Studied by Hydrogen/Deuterium Exchange

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ACCOUNTS OF CHEMICAL RESEARCH (2010)

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Quantitative and spatio-temporal features of protein aggregation in Escherichia coli and consequences on protein quality control and cellular ageing

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EMBO JOURNAL (2010)

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A bioreactor for in-cell protein NMR

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JOURNAL OF MAGNETIC RESONANCE (2010)

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Guidelines for the use of band-selective radiofrequency pulses in hetero-nuclear NMR: Example of longitudinal-relaxation-enhanced BEST-type 1H-15N correlation experiments

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JOURNAL OF MAGNETIC RESONANCE (2010)

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Protein 19F NMR in Escherichia coli

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JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2010)

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Highly sensitive amyloid detection enabled by thioflavin T dimers

Luoheng Qin et al.

MOLECULAR BIOSYSTEMS (2010)

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Protein folding stability and dynamics imaged in a living cell

Simon Ebbinghaus et al.

NATURE METHODS (2010)

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Thioflavine T interaction with synthetic Alzheimer's disease β-amyloid peptides: Detection of amyloid aggregation in solution

Harry Levine

PROTEIN SCIENCE (2010)

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In vivo near-infrared fluorescence imaging of cancer with nanoparticle-based probes

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WILEY INTERDISCIPLINARY REVIEWS-NANOMEDICINE AND NANOBIOTECHNOLOGY (2010)

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Observation of NMR Signals from Proteins Introduced into Living Mammalian Cells by Reversible Membrane Permeabilization Using a Pore-Forming Toxin, Streptolysin O

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JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2009)

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Design, Synthesis, and Testing of Difluoroboron-Derivatized Curcumins as Near-Infrared Probes for in Vivo Detection of Amyloid-β Deposits

Chongzhao Ran et al.

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2009)

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Protein structure determination in living cells by in-cell NMR spectroscopy

Daisuke Sakakibara et al.

NATURE (2009)

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High-resolution multi-dimensional NMR spectroscopy of proteins in human cells

Kohsuke Inomata et al.

NATURE (2009)

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Seeded growth of β-amyloid fibrils from Alzheimer's brain-derived fibrils produces a distinct fibril structure

Anant K. Paravastu et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2009)

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Thermodynamic analysis of protein stability and ligand binding using a chemical modification- and mass-spectrometry based strategy

Graham M. West et al.

ANALYTICAL CHEMISTRY (2008)

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Differential dynamical effects of macromolecular crowding on an intrinsically disordered protein and a globular protein: Implications for in-cell NMR spectroscopy

Conggang Li et al.

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2008)

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Molecular structural basis for polymorphism in Alzheimer's β-amyloid fibrils

Anant K. Paravastu et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2008)

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Hydrogen exchange of monomeric α-synuclein shows unfolded structure persists at physiological temperature and is independent of molecular crowding in Escherichia coli

Robyn L. Croke et al.

PROTEIN SCIENCE (2008)

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Adapting proteostasis for disease intervention

William E. Balch et al.

SCIENCE (2008)

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Mutant SOD1 detoxification mechanisms in intact single cells

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CELL DEATH AND DIFFERENTIATION (2008)

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Correlative microscopy: Bridging the gap between fluorescence light microscopy and cryo-electron tomography

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JOURNAL OF STRUCTURAL BIOLOGY (2007)

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Atomic structures of amyloid cross-β spines reveal varied steric zippers

Michael R. Sawaya et al.

NATURE (2007)

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β-Sheet core of human prion protein amyloid fibrils as determined by hydrogen/deuterium exchange

Xiaojun Lu et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2007)

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TDP-43 is a component of ubiquitin-positive tau-negative inclusions in frontotemporal lobar degeneration and amyotrophic lateral sclerosis

Tetsuaki Arai et al.

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (2006)

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In-cell NMR spectroscopy of proteins inside Xenopus laevis oocytes

Tomomi Sakai et al.

JOURNAL OF BIOMOLECULAR NMR (2006)

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Ubiquitinated TDP-43 in frontotemporal lobar degeneration and amyotrophic lateral sclerosis

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SCIENCE (2006)

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Structural differences in Aβ amyloid protofibrils and fibrils mapped by hydrogen exchange -: Mass spectrometry with on-line proteolytic fragmentation

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JOURNAL OF MOLECULAR BIOLOGY (2006)

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Quantitative NMR analysis of the protein G B1 domain in Xenopus laevis egg extracts and intact oocytes

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2006)

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Macromolecular crowding in the Escherichia coli periplasm maintains α-synuclein disorder

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JOURNAL OF MOLECULAR BIOLOGY (2006)

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Secondary structure of α-synuclein oligomers:: Characterization by Raman and atomic force microscopy

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JOURNAL OF MOLECULAR BIOLOGY (2006)

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Investigating macromolecules inside cultured and injected cells by in-cell NMR spectroscopy

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NATURE PROTOCOLS (2006)

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SOFAST-HMQC experiments for recording two-dimensional heteronuclear correlation spectra of proteins within a few seconds

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JOURNAL OF BIOMOLECULAR NMR (2005)

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Laser flash photolysis of hydrogen peroxide to oxidize protein solvent-accessible residues on the microsecond timescale

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JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY (2005)

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Probing PrPSc structure using chemical cross-linking and mass spectrometry:: Evidence of the proximity of Gly90 amino termini in the PrP 27-30 aggregate

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BIOCHEMISTRY (2005)

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In vivo detection of amyloid-β deposits by near-infrared imaging using an oxazine-derivative probe

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NATURE BIOTECHNOLOGY (2005)

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NMR studies of protein structure and dynamics

LE Kay

JOURNAL OF MAGNETIC RESONANCE (2005)

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Unfolding, aggregation, and seeded amyloid formation of lysine-58-cleaved β2-microglobulin

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BIOCHEMISTRY (2005)

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Intrinsically unstructured proteins and their functions

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NATURE REVIEWS MOLECULAR CELL BIOLOGY (2005)

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Monitoring protein stability and aggregation in vivo by real-time fluorescent labeling

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PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2004)

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NMR characterization of the dynamics of biomacromolecules

AG Palmer

CHEMICAL REVIEWS (2004)

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Biophysical characterization of the free IκBα ankyrin repeat domain in solution

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Methyl groups as probes for proteins and complexes in in-cell NMR experiments

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JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2004)

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Emerging principles of conformation based prion inheritance

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ANNUAL REVIEW OF BIOCHEMISTRY (2004)

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Protein folding and misfolding

CM Dobson

NATURE (2003)

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Nuclear magnetic resonance spectroscopy reveals the functional state of the signalling protein CheY in vivo in Escherichia coli

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MOLECULAR MICROBIOLOGY (2003)

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Longitudinal 1H relaxation optimization in TROSY NMR spectroscopy

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JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2002)

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Uncharged thioflavin-T derivatives bind to amyloid-beta protein with high affinity and readily enter the brain

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LIFE SCIENCES (2001)

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Alpha-synuclein and neurodegenerative diseases

M Goedert

NATURE REVIEWS NEUROSCIENCE (2001)

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High-resolution macromolecular NMR spectroscopy inside living cells

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JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2001)

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Review: History of the amyloid fibril

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JOURNAL OF STRUCTURAL BIOLOGY (2000)

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