4.8 Review

Protein Oligomer Engineering: A New Frontier for Studying Protein Structure, Function, and Toxicity

Related references

Note: Only part of the references are listed.
Article Multidisciplinary Sciences

Combinatorial assembly and design of enzymes

R. Lipsh-Sokolik et al.

Summary: An atomistic and machine learning strategy called CADENZ was used to design enzyme fragments that combine to form diverse, low-energy structures with stable catalytic configurations. This strategy was applied to endoxylanases and resulted in the recovery of thousands of structurally diverse enzymes using activity-based protein profiling. Functional designs showed high active-site preorganization and more stable and compact packing outside the active site. Implementing these findings into CADENZ led to a 10-fold improved hit rate and over 10,000 recovered enzymes. This design-test-learn loop can be applied to any modular protein family, providing vast diversity and general principles for protein design.

SCIENCE (2023)

Article Chemistry, Multidisciplinary

Single-molecule nanopore dielectrophoretic trapping of a-synuclein with lipid membranes

Jinming Wu et al.

Summary: In this study, the lipid-binding and-unbinding kinetics of a-Syn in an aHL single nanopore were investigated, revealing the conformational switch events of a-Syn and its interactions with disease-associated metal ions and helical peptidomimetics. These findings contribute to our understanding of the complex interplay between a-Syn, lipid membranes, and metal ions, and provide a new strategy for combating a-Syn toxicity and aggregation using peptidomimetics.

CELL REPORTS PHYSICAL SCIENCE (2023)

Article Chemistry, Multidisciplinary

Multivariate effects of pH, salt, and Zn2+ ions on Aβ40 fibrillation

Hongzhi Wang et al.

Summary: Amyloid-beta (A beta) peptide aggregation is pivotal in Alzheimer's disease (AD), which is characterized by the formation of A beta-deposited extracellular amyloid plaques. The brain microenvironmental changes in AD patients, such as local acidification, increased ionic strength, or altered metal ion levels, collectively modulate the aggregation of A beta peptides. This study investigates the multivariate effects of varied pH, ionic strength, and Zn2+ on A beta(40) fibrillation kinetics. The findings demonstrate that pH and ionic strength strongly affect A beta fibrillation kinetics, underscoring the importance of electrostatic interactions in regulating A beta(40) fibrillation. Additionally, the presence of Zn2+ ions can further alter or even reverse the role of pH and ionic strength on the amyloid fibril kinetics, highlighting the significance of amino acids like Histidine that can interact with Zn2+ ions. Furthermore, both pH and ionic strength regulate the secondary nucleation processes, while irrespective of pH and Zn2+ ions, ionic strength can also modulate the morphology of A beta(40) aggregates. These multivariate effects provide insights into the correlation between pH, ionic strength, or Zn2+ ion changes with amyloid deposits in the AD brain, deepening our understanding of the molecular pathology in the local brain microenvironment.

COMMUNICATIONS CHEMISTRY (2022)

Review Pharmacology & Pharmacy

When Natural Compounds Meet Nanotechnology: Nature-Inspired Nanomedicines for Cancer Immunotherapy

Linna Yu et al.

Summary: This article summarizes the immune regulatory mechanisms of natural compounds in different stages of the cancer-immunity cycle and introduces various drug delivery strategies based on nanotechnology to overcome their limitations in biomedical applications. The representative applications of nature-inspired nanomedicines are emphasized, and their advantages and disadvantages are discussed. Finally, the challenges and prospects of natural compounds for cancer immunotherapy are provided.

PHARMACEUTICS (2022)

Review Biochemistry & Molecular Biology

Therapeutic peptides: current applications and future directions

Lei Wang et al.

Summary: Peptide drug development has achieved significant progress in the past decade, thanks to new production, modification, and analytic technologies. These advancements have addressed the inherent limitations of peptides and have resulted in achievements in various therapeutic areas.

SIGNAL TRANSDUCTION AND TARGETED THERAPY (2022)

Article Biochemistry & Molecular Biology

Visualizing and trapping transient oligomers in amyloid assembly pathways

Emma E. Cawood et al.

Summary: Understanding the formation and toxicity mechanisms of oligomers during amyloid fibril assembly is crucial for amyloid diseases. By utilizing methods such as NMR, mass spectrometry, and tools to manipulate the amyloid energy landscape, researchers can gain insights into the nature and role of these oligomeric intermediates. These approaches allow for the study of kinetics, structural information, and structure-toxicity relationships of oligomers, providing a clearer picture of their contribution to amyloid formation and disease.

BIOPHYSICAL CHEMISTRY (2021)

Review Biotechnology & Applied Microbiology

Engineering precision nanoparticles for drug delivery

Michael J. Mitchell et al.

Summary: The development of nanoparticles has shown promising clinical applications, overcoming the limitations of therapeutic interventions and biological barriers. Precision therapies have enhanced treatment efficacy through personalized interventions. Advancements in nanoparticle design aim to optimize drug delivery, improving efficacy in general applications and enabling tailored designs for precision applications.

NATURE REVIEWS DRUG DISCOVERY (2021)

Article Biology

Properdin oligomers adopt rigid extended conformations supporting function

Dennis Pedersen et al.

Summary: Properdin stabilizes convertases in the complement cascade and its biological activity depends on its oligomerization state. Properdin oligomers adopt extended rigid conformations approximated by single models of apparent n-fold rotational symmetry. Multivalency alone is insufficient for full activity in a cell lysis assay, indicating that the observed oligomer structure is essential for Properdin function.

ELIFE (2021)

Article Multidisciplinary Sciences

De novo protein design by deep network hallucination

Ivan Anishchenko et al.

Summary: Recent progress in protein structure prediction using deep neural networks has shown that these networks can be used to design new proteins with novel functions, by generating new folded proteins with sequences unrelated to those of naturally occurring proteins.

NATURE (2021)

Article Multidisciplinary Sciences

Computed structures of core eukaryotic protein complexes

Ian R. Humphreys et al.

Summary: By utilizing proteome-wide amino acid coevolution analysis and deep-learning-based structure modeling, we systematically identified and built accurate models of core eukaryotic protein complexes within the Saccharomyces cerevisiae proteome. These models cover nearly 800 previously uncharacterized assemblies, providing comprehensive insights into key processes in eukaryotic cells.

SCIENCE (2021)

Article Chemistry, Multidisciplinary

Cryo-electron Microscopy Imaging of Alzheimer's Amyloid-beta 42 Oligomer Displayed on a Functionally and Structurally Relevant Scaffold

Jinming Wu et al.

Summary: Amyloid-beta peptide (Aβ) oligomers are pathogenic aggregates in Alzheimer's disease, which can permeabilize cellular membranes through a pore formation mechanism. The Aβ42-αHL oligomers share major structural, functional, and biological properties with wild-type Aβ42-pores, with the pore region being intrinsically flexible according to single-particle cryo-EM analysis. Aβ42-αHL oligomers could be a highly specific antigen for immuno-based diagnostics and therapies, allowing for the study of features of wild-type amyloid oligomers.

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION (2021)

Article Multidisciplinary Sciences

Highly accurate protein structure prediction with AlphaFold

John Jumper et al.

Summary: Proteins are essential for life, and accurate prediction of their structures is a crucial research problem. Current experimental methods are time-consuming, highlighting the need for accurate computational approaches to address the gap in structural coverage. Despite recent progress, existing methods fall short of atomic accuracy in protein structure prediction.

NATURE (2021)

Article Multidisciplinary Sciences

Accurate prediction of protein structures and interactions using a three-track neural network

Minkyung Baek et al.

Summary: Through the three-track network, we achieved accuracies approaching those of DeepMind in CASP14, enabling rapid solution of challenging x-ray crystallography and cryo-electron microscopy structure modeling problems, and providing insights into the functions of proteins with currently unknown structure.

SCIENCE (2021)

Article Biochemistry & Molecular Biology

Revealing the Specificity of a Range of Antimicrobial Peptides in Lipid Nanodiscs by Native Mass Spectrometry

Lawrence R. Walker et al.

BIOCHEMISTRY (2020)

Review Pharmacology & Pharmacy

Protein-Based Nanoparticles as Drug Delivery Systems

Seyoung Hong et al.

PHARMACEUTICS (2020)

Article Biochemistry & Molecular Biology

Multifunctional Amyloid Oligomeric Nanoparticles for Specific Cell Targeting and Drug Delivery

Weiqiang Wang et al.

BIOMACROMOLECULES (2020)

Review Biochemistry & Molecular Biology

Progress toward Alzheimer's disease treatment: Leveraging the Achilles' heel of Aβ oligomers?

Jacques Fantini et al.

PROTEIN SCIENCE (2020)

Article Multidisciplinary Sciences

Aβ(1-42) tetramer and octamer structures reveal edge conductivity pores as a mechanism for membrane damage

Sonia Ciudad et al.

NATURE COMMUNICATIONS (2020)

Article Multidisciplinary Sciences

Computational design of transmembrane pores

Chunfu Xu et al.

NATURE (2020)

Article Multidisciplinary Sciences

Quantifying the distribution of protein oligomerization degree reflects cellular information capacity

Lena Danielli et al.

SCIENTIFIC REPORTS (2020)

Review Medicine, Research & Experimental

Structure-Based Vaccine Antigen Design

Barney S. Graham et al.

ANNUAL REVIEW OF MEDICINE, VOL 70 (2019)

Article Chemistry, Multidisciplinary

Templated Assembly of Pore-forming Peptides in Lipid Membranes

Aziz Fennouri et al.

CHIMIA (2019)

Review Biochemistry & Molecular Biology

Modulation of protein oligomerization: An overview

Neha Kumari et al.

PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY (2019)

Article Biochemistry & Molecular Biology

Protein oligomerization as a metabolic control mechanism: Application to apoE

Carl Frieden

PROTEIN SCIENCE (2019)

Review Pharmacology & Pharmacy

Alginate Nanoparticles for Drug Delivery and Targeting

Patricia Severino et al.

CURRENT PHARMACEUTICAL DESIGN (2019)

Article Chemistry, Multidisciplinary

Native Ion Mobility-Mass Spectrometry Reveals the Formation of β-Barrel Shaped Amyloid-β Hexamers in a Membrane-Mimicking Environment

Nicklas Osterlund et al.

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2019)

Article Biochemistry & Molecular Biology

Fusion of DARPin to Aldolase Enables Visualization of Small Protein by Cryo-EM

Qing Yao et al.

STRUCTURE (2019)

Review Nanoscience & Nanotechnology

Alzheimer's disease: pathogenesis, diagnostics, and therapeutics

Sneham Tiwari et al.

INTERNATIONAL JOURNAL OF NANOMEDICINE (2019)

Review Biochemistry & Molecular Biology

Better together: building protein oligomers naturally and by design

Rebecca E. A. Gwyther et al.

BIOCHEMICAL SOCIETY TRANSACTIONS (2019)

Review Microbiology

Mechanisms of Action for Antimicrobial Peptides With Antibacterial and Antibiofilm Functions

Nigare Raheem et al.

FRONTIERS IN MICROBIOLOGY (2019)

Review Chemistry, Multidisciplinary

Peptide and protein nanoparticle conjugates: versatile platforms for biomedical applications

Christopher D. Spicer et al.

CHEMICAL SOCIETY REVIEWS (2018)

Article Nanoscience & Nanotechnology

DNA scaffolds support stable and uniform peptide nanopores

Evan Spruijt et al.

NATURE NANOTECHNOLOGY (2018)

Article Multidisciplinary Sciences

Near-atomic cryo-EM imaging of a small protein displayed on a designed scaffolding system

Yuxi Liu et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2018)

Article Multidisciplinary Sciences

Accurate computational design of multipass transmembrane proteins

Peilong Lu et al.

SCIENCE (2018)

Article Multidisciplinary Sciences

De novo design of a fluorescence-activating β-barrel

Jiayi Dou et al.

NATURE (2018)

Article Biochemistry & Molecular Biology

De novo design of a non-local β-sheet protein with high stability and accuracy

Enrique Marcos et al.

NATURE STRUCTURAL & MOLECULAR BIOLOGY (2018)

Article Chemistry, Multidisciplinary

A monodisperse transmembrane α-helical peptide barrel

Kozhinjampara R. Mahendran et al.

NATURE CHEMISTRY (2017)

Article Multidisciplinary Sciences

Serum amyloid A forms stable oligomers that disrupt vesicles at lysosomal pH and contribute to the pathogenesis of reactive amyloidosis

Shobini Jayaraman et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2017)

Review Biotechnology & Applied Microbiology

Advances in Alzheimer's Diagnosis and Therapy: The Implications of Nanotechnology

Mohammad Javad Hajipour et al.

TRENDS IN BIOTECHNOLOGY (2017)

Article Multidisciplinary Sciences

Discovery and characterization of stable and toxic Tau/phospholipid oligomeric complexes

Nadine Ait-Bouziad et al.

NATURE COMMUNICATIONS (2017)

Review Biochemistry & Molecular Biology

Current state of a dual behaviour of antimicrobial peptidesTherapeutic agents and promising delivery vectors

Urszula Piotrowska et al.

CHEMICAL BIOLOGY & DRUG DESIGN (2017)

Meeting Abstract Biophysics

Targeting Specific Membranes with the Pore-Forming Peptide Ceratotoxin a using Click Chemistry

Simon F. Mayer et al.

BIOPHYSICAL JOURNAL (2017)

Review Chemistry, Multidisciplinary

Towards an understanding of amyloid-β oligomers: characterization, toxicity mechanisms, and inhibitors

Shin Jung C. Lee et al.

CHEMICAL SOCIETY REVIEWS (2017)

Article Biochemistry & Molecular Biology

De novo design of a four-fold symmetric TIM-barrel protein with atomic-level accuracy

Po-Ssu Huang et al.

NATURE CHEMICAL BIOLOGY (2016)

Article Biochemistry & Molecular Biology

Soluble Oligomers of PolyQ-Expanded Huntingtin Target a Multiplicity of Key Cellular Factors

Yujin E. Kim et al.

MOLECULAR CELL (2016)

Article Multidisciplinary Sciences

Aβ42 assembles into specific β-barrel pore-forming oligomers in membrane-mimicking environments

Montserrat Serra-Batiste et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2016)

Review Clinical Neurology

Amyloid β oligomers in Alzheimer's disease pathogenesis, treatment, and diagnosis

Kirsten L. Viola et al.

ACTA NEUROPATHOLOGICA (2015)

Review Clinical Neurology

Toxic species in amyloid disorders: Oligomers or mature fibrils

Meenakshi Verma et al.

ANNALS OF INDIAN ACADEMY OF NEUROLOGY (2015)

Review Biochemistry & Molecular Biology

Structural, morphological, and functional diversity of amyloid oligomers

Leonid Breydo et al.

FEBS LETTERS (2015)

Article Cell Biology

α-synuclein and synapsin III cooperatively regulate synaptic function in dopamine neurons

Michela Zaltieri et al.

JOURNAL OF CELL SCIENCE (2015)

Article Neurosciences

Three dimensions of the amyloid hypothesis: time, space and 'wingmen'

Erik S. Musiek et al.

NATURE NEUROSCIENCE (2015)

Review Nanoscience & Nanotechnology

Structure and function of G protein-coupled receptor oligomers: implications for drug discovery

Nicole S. Schonenbach et al.

WILEY INTERDISCIPLINARY REVIEWS-NANOMEDICINE AND NANOBIOTECHNOLOGY (2015)

Review Biochemistry & Molecular Biology

Hemoprotein-based supramolecular assembling systems

Koji Oohora et al.

CURRENT OPINION IN CHEMICAL BIOLOGY (2014)

Article Biochemistry & Molecular Biology

Structural Insights into Amyloid Oligomers of the Parkinson Disease-related Protein α-Synuclein

J. Ignacio Gallea et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2014)

Article Chemistry, Multidisciplinary

The Role of Stable α-Synuclein Oligomers in the Molecular Events Underlying Amyloid Formation

Nikolai Lorenzen et al.

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2014)

Article Chemistry, Multidisciplinary

The Presence of an Air-Water Interface Affects Formation and Elongation of α-Synuclein Fibrils

Silvia Campioni et al.

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2014)

Review Neurosciences

Oligomeric Aβ-induced synaptic dysfunction in Alzheimer's disease

Shichun Tu et al.

MOLECULAR NEURODEGENERATION (2014)

Article Chemistry, Multidisciplinary

The A beta peptide forms non-amyloid fibrils in the presence of carbon nanotubes

Jinghui Luo et al.

NANOSCALE (2014)

Review Chemistry, Multidisciplinary

Allosteric modulation of protein oligomerization: an emerging approach to drug design

Ronen Gabizon et al.

FRONTIERS IN CHEMISTRY (2014)

Article Multidisciplinary Sciences

Quantitative analysis of the time course of Aβ oligomerization and subsequent growth steps using tetramethylrhodamine-labeled Aβ

Kanchan Garai et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2013)

Article Multidisciplinary Sciences

Proliferation of amyloid-β42 aggregates occurs through a secondary nucleation mechanism

Samuel I. A. Cohen et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2013)

Article Multidisciplinary Sciences

An engineered dimeric protein pore that spans adjacent lipid bilayers

Shiksha Mantri et al.

NATURE COMMUNICATIONS (2013)

Article Biochemistry & Molecular Biology

Toxic prefibrillar α-synuclein amyloid oligomers adopt a distinctive antiparallel β-sheet structure

Maria Soledad Celej et al.

BIOCHEMICAL JOURNAL (2012)

Article Chemistry, Physical

Cyclodextrin-Scaffolded Alamethicin with Remarkably Efficient Membrane Permeabilizing Properties and Membrane Current Conductance

Claudia U. Hjorringgaard et al.

JOURNAL OF PHYSICAL CHEMISTRY B (2012)

Review Neurosciences

The toxic Aβ oligomer and Alzheimer's disease: an emperor in need of clothes

Iryna Benilova et al.

NATURE NEUROSCIENCE (2012)

Article Multidisciplinary Sciences

Specific Recognition of p53 Tetramers by Peptides Derived from p53 Interacting Proteins

Ronen Gabizon et al.

PLOS ONE (2012)

Review Biochemistry & Molecular Biology

Role of lipids in the interaction of antimicrobial peptides with membranes

Vitor Teixeira et al.

PROGRESS IN LIPID RESEARCH (2012)

Review Biochemistry & Molecular Biology

Structure and Pharmacology of Pentameric Receptor Channels: From Bacteria to Brain

Pierre-Jean Corringer et al.

STRUCTURE (2012)

Article Medicine, Research & Experimental

Treatment Strategies Targeting Amyloid β-Protein

Dale Schenk et al.

COLD SPRING HARBOR PERSPECTIVES IN MEDICINE (2012)

Article Biochemistry & Molecular Biology

In search of a novel target - Phosphatidylserine exposed by non-apoptotic tumor cells and metastases of malignancies with poor treatment efficacy

Sabrina Riedl et al.

BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES (2011)

Article Chemistry, Physical

Influence of Nanoparticle Size and Shape on Oligomer Formation of an Amyloidogenic Peptide

Edward P. O'Brien et al.

JOURNAL OF PHYSICAL CHEMISTRY LETTERS (2011)

Article Biochemistry & Molecular Biology

The Positively Charged Region of the Myosin IIC Non-helical Tailpiece Promotes Filament Assembly

Daniel Ronen et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2010)

Article Multidisciplinary Sciences

Mechanisms of protein oligomerization, the critical role of insertions and deletions in maintaining different oligomeric states

Kosuke Hashimoto et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2010)

Review Biochemistry & Molecular Biology

Reassessing the amyloid cascade hypothesis of Alzheimer's disease

Sanjay W. Pimplikar

INTERNATIONAL JOURNAL OF BIOCHEMISTRY & CELL BIOLOGY (2009)

Review Biochemistry & Molecular Biology

Protein oligomerization in the bacterial outer membrane

Guoyu Meng et al.

MOLECULAR MEMBRANE BIOLOGY (2009)

Article Biochemistry & Molecular Biology

Structures of Human Host Defense Cathelicidin LL-37 and Its Smallest Antimicrobial Peptide KR-12 in Lipid Micelles

Guangshun Wang

JOURNAL OF BIOLOGICAL CHEMISTRY (2008)

Article Chemistry, Multidisciplinary

Inhibition of Amyloid β Protein Fibrillation by Polymeric Nanoparticles

Celia Cabaleiro-Lago et al.

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2008)

Article Neurosciences

Different species of α-synuclein oligomers induce calcium influx and seeding

Karin M. Danzer et al.

JOURNAL OF NEUROSCIENCE (2007)

Article Multidisciplinary Sciences

Inhibiting HIV-1 integrase by shifting its oligomerization equilibrium

Zvi Hayouka et al.

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

Article Nanoscience & Nanotechnology

Structure-based design of peptides that self-assemble into regular polyhedral nanoparticles

Senthilkumar Raman et al.

NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE (2006)

Article Geriatrics & Gerontology

Common mechanisms of amyloid oligomer pathogenesis in degenerative disease

CG Glabe

NEUROBIOLOGY OF AGING (2006)

Article Multidisciplinary Sciences

Molecular tuning of fast gating in pentameric ligand-gated ion channels

T Grutter et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2005)

Review Oncology

Pyruvate kinase type M2 and its role in tumor growth and spreading

S Mazurek et al.

SEMINARS IN CANCER BIOLOGY (2005)

Review Multidisciplinary Sciences

Allosteric mechanisms of signal transduction

JP Changeux et al.

SCIENCE (2005)

Review Microbiology

Antimicrobial peptides: Pore formers or metabolic inhibitors in bacteria?

KA Brogden

NATURE REVIEWS MICROBIOLOGY (2005)

Review Biochemistry & Molecular Biology

Protein oligomerization: How and why

MH Ali et al.

BIOORGANIC & MEDICINAL CHEMISTRY (2005)