4.7 Article

Different Intermolecular Interactions Drive Nonpathogenic Liquid-Liquid Phase Separation and Potentially Pathogenic Fibril Formation by TDP-43

Related references

Note: Only part of the references are listed.
Review Biochemistry & Molecular Biology

Liquid-liquid phase separation as an organizing principle of intracellular space: overview of the evolution of the cell compartmentalization concept

Iuliia A. Antifeeva et al.

Summary: Fundamental changes took place in the understanding of protein structure and function, as well as the organization of intracellular space, at the turn of the twenty-first century. The traditional mechanistic model was replaced by the idea of dynamic and multifunctional soft matter playing a central role. Liquid-liquid phase transitions of biopolymers were identified as crucial for spatio-temporal organization. Changes in external conditions could disrupt cellular bodies' formation and lead to the emergence of amyloid fibrils.

CELLULAR AND MOLECULAR LIFE SCIENCES (2022)

Article Biochemistry & Molecular Biology

Sequence Determinants of the Aggregation of Proteins Within Condensates Generated by Liquid-liquid Phase Separation

Michele Vendruscolo et al.

Summary: This study investigates the sequence determinants of protein aggregation via the condensation pathway and identifies three relevant features: droplet-promoting propensity, aggregation-promoting propensity, and multimodal interactions quantified by the binding mode entropy. By using this approach, aggregation-promoting mutations in droplet-forming proteins associated with amyotrophic lateral sclerosis (ALS) can be predicted.

JOURNAL OF MOLECULAR BIOLOGY (2022)

Review Multidisciplinary Sciences

Protein condensation diseases: therapeutic opportunities

Michele Vendruscolo et al.

Summary: Condensed states of proteins play crucial roles in the organization and function of cells, and disruptions of these states can lead to various diseases. This review analyzes the identification of targets for pharmacological interventions and explores opportunities for regulating aberrant protein condensation.

NATURE COMMUNICATIONS (2022)

Review Chemistry, Multidisciplinary

Fuzziness and Frustration in the Energy Landscape of Protein Folding, Function, and Assembly

Stefano Gianni et al.

Summary: Proteins and their complexes can be described as ensembles that populate an energy landscape, where the diversity arises from the conflicts between interactions shaping the energy landscape. Within this framework, alternative sets of suboptimal contacts can encode specificity without achieving a single structural optimum. The interplay between frustration and fuzziness offers insights into the structural and dynamical continuum of protein assemblies.

ACCOUNTS OF CHEMICAL RESEARCH (2021)

Review Neurosciences

Triad of TDP43 control in neurodegeneration: autoregulation, localization and aggregation

Paraskevi Tziortzouda et al.

Summary: The abnormal expression and cytoplasmic aggregation of TDP43, along with its nuclear loss, are characteristic features of neurodegenerative diseases. Autoregulation, nucleocytoplasmic transport, and phase transition are three intrinsic mechanisms that control the levels and localization of TDP43, essential for cellular homeostasis and affected in pathology.

NATURE REVIEWS NEUROSCIENCE (2021)

Article Biochemistry & Molecular Biology

Phe-Gly motifs drive fibrillization of TDP-43's prion-like domain condensates

David Pantoja-Uceda et al.

Summary: TDP-43 can form various aggregate forms, with droplets potentially evolving into fibrils or remaining in droplet form, influenced by different factors. Research unexpectedly observed droplet formation in the absence of salts or RNAs, visual evidence of fibrillization at the droplet surface/solvent interface, highlighting the key role of Phe-Gly motifs in fibril core formation.

PLOS BIOLOGY (2021)

Article Biochemistry & Molecular Biology

Liquid-Liquid Phase Separation Enhances TDP-43 LCD Aggregation but Delays Seeded Aggregation

Donya Pakravan et al.

Summary: This study investigated how phase separation affects the aggregation of TDP-43 protein, finding that liquid-liquid phase separation (LLPS) promotes spontaneous aggregation but hinders seeded aggregation. Analysis of various conditions using buffers showed that stabilizing hydrophobic interactions are more important than destabilizing electrostatic forces. RNA was found to affect the cooperativity between LLPS and aggregation in a reentrant manner.

BIOMOLECULES (2021)

Review Biochemistry & Molecular Biology

Liquid-liquid phase separation in human health and diseases

Bin Wang et al.

Summary: LLPS plays a vital role in the formation of membraneless organelles, physiological functions, and disease development. Advances in research methods provide opportunities for deeper understanding of LLPS. It is crucial to stay informed about recent developments in the field to translate current knowledge into therapeutic discoveries.

SIGNAL TRANSDUCTION AND TARGETED THERAPY (2021)

Article Chemistry, Multidisciplinary

Solid-State NMR Reveals the Structural Transformation of the TDP-43 Amyloidogenic Region upon Fibrillation

Xiao-Feng Zhuo et al.

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2020)

Article Multidisciplinary Sciences

TDP-43 α-helical structure tunes liquid-liquid phase separation and function

Alexander E. Conicella et al.

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

Article Biochemistry & Molecular Biology

Hydroxyapatite Formation Coexists with Amyloid-like Self-Assembly of Human Amelogenin

Jing Zhang et al.

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES (2020)

Article Neurosciences

RNA Binding Antagonizes Neurotoxic Phase Transitions of TDP-43

Jacob R. Mann et al.

NEURON (2019)

Article Multidisciplinary Sciences

Structural basis for reversible amyloids of hnRNPA1 elucidates their role in stress granule assembly

Xinrui Gui et al.

NATURE COMMUNICATIONS (2019)

Review Neurosciences

Structural Insights Into TDP-43 and Effects of Post-translational Modifications

Liberty Francois-Moutal et al.

FRONTIERS IN MOLECULAR NEUROSCIENCE (2019)

Article Biochemistry & Molecular Biology

The physical forces mediating self-association and phase-separation in the C-terminal domain of TDP-43

Hao-Ru Li et al.

BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS (2018)

Article Biochemistry & Molecular Biology

Atomic structures of TDP-43 LCD segments and insights into reversible or pathogenic aggregation

Elizabeth L. Guenther et al.

NATURE STRUCTURAL & MOLECULAR BIOLOGY (2018)

Article Biochemistry & Molecular Biology

Atomic structures of TDP-43 LCD segments and insights into reversible or pathogenic aggregation

Elizabeth L. Guenther et al.

NATURE STRUCTURAL & MOLECULAR BIOLOGY (2018)

Review Cell Biology

Biomolecular condensates: organizers of cellular biochemistry

Salman F. Banani et al.

NATURE REVIEWS MOLECULAR CELL BIOLOGY (2017)

Article Biochemistry & Molecular Biology

Phase to Phase with TDP-43

Yulong Sun et al.

BIOCHEMISTRY (2017)

Editorial Material Biochemistry & Molecular Biology

Electrostatic Repulsion Governs TDP-43 C-terminal Domain Aggregation

Miguel Mompean et al.

PLOS BIOLOGY (2016)

Article Biochemistry & Molecular Biology

A Liquid-to-Solid Phase Transition of the ALS Protein FUS Accelerated by Disease Mutation

Avinash Patel et al.

Article Chemistry, Physical

Structural Evidence of Amyloid Fibril Formation in the Putative Aggregation Domain of TDP-43

Miguel Mompean et al.

JOURNAL OF PHYSICAL CHEMISTRY LETTERS (2015)

Review Cell & Tissue Engineering

Polyglutamine (PolyQ) Diseases: Genetics to Treatments

Hueng-Chuen Fan et al.

CELL TRANSPLANTATION (2014)

Review Pharmacology & Pharmacy

Fusion protein linkers: Property, design and functionality

Xiaoying Chen et al.

ADVANCED DRUG DELIVERY REVIEWS (2013)

Article Biochemistry & Molecular Biology

Resolution of Oligomeric Species during the Aggregation of Aβ1-40 Using 19F NMR

Yuta Suzuki et al.

BIOCHEMISTRY (2013)

Article Biochemistry & Molecular Biology

Structural Transformation of the Amyloidogenic Core Region of TDP-43 Protein Initiates Its Aggregation and Cytoplasmic Inclusion

Lei-Lei Jiang et al.

JOURNAL OF BIOLOGICAL CHEMISTRY (2013)

Article Chemistry, Multidisciplinary

Dynamic Equilibria between Monomeric and Oligomeric Misfolded States of the Mammalian Prion Protein Measured by F-19 NMR

Sacha Thierry Larda et al.

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2013)

Review Cell Biology

Cajal bodies: where form meets function

Martin Machyna et al.

WILEY INTERDISCIPLINARY REVIEWS-RNA (2013)

Review Neurosciences

TDP-43 aggregation in neurodegeneration: Are stress granules the key?

Colleen M. Dewey et al.

BRAIN RESEARCH (2012)

Review Biochemistry & Molecular Biology

Eukaryotic Stress Granules: The Ins and Outs of Translation

J. Ross Buchan et al.

MOLECULAR CELL (2009)

Article Multidisciplinary Sciences

Germline P Granules Are Liquid Droplets That Localize by Controlled Dissolution/Condensation

Clifford P. Brangwynne et al.

SCIENCE (2009)

Article Cell Biology

A role for Q/N-rich aggregation-prone regions in P-body localization

Martin A. M. Reijns et al.

JOURNAL OF CELL SCIENCE (2008)