On the Structural Diversity and Individuality of Polymorphic Amyloid Protein Assemblies DOI
Liisa Lutter, Liam D. Aubrey, Wei‐Feng Xue

et al.

Journal of Molecular Biology, Journal Year: 2021, Volume and Issue: 433(20), P. 167124 - 167124

Published: July 2, 2021

Language: Английский

Half a century of amyloids: past, present and future DOI Creative Commons
Pu Chun Ke, Ruhong Zhou, Louise C. Serpell

et al.

Chemical Society Reviews, Journal Year: 2020, Volume and Issue: 49(15), P. 5473 - 5509

Published: Jan. 1, 2020

Amyloid diseases are global epidemics with profound health, social and economic implications yet remain without a cure. This dire situation calls for research into the origin pathological manifestations of amyloidosis to stimulate continued development new therapeutics. In basic science engineering, cross-β architecture has been constant thread underlying structural characteristics functional amyloids, realizing that amyloid structures can be both in nature fuelled innovations artificial whose use today ranges from water purification 3D printing. At conclusion half century since Eanes Glenner's seminal study amyloids humans, this review commemorates occasion by documenting major milestones date, perspectives biology, biophysics, medicine, microbiology, engineering nanotechnology. We also discuss challenges opportunities drive interdisciplinary field moving forward.

Language: Английский

Citations

476
The expanding amyloid family: Structure, stability, function, and pathogenesis DOI Creative Commons
M.R. Sawaya, Michael P. Hughes,

José A. Rodríguez

et al.

Cell, Journal Year: 2021, Volume and Issue: 184(19), P. 4857 - 4873

Published: Sept. 1, 2021

Language: Английский

Citations

270
Amyloid-type Protein Aggregation and Prion-like Properties of Amyloids DOI Creative Commons
Dieter Willbold, Birgit Strodel, Gunnar F. Schröder

et al.

Chemical Reviews, Journal Year: 2021, Volume and Issue: 121(13), P. 8285 - 8307

Published: June 17, 2021

This review will focus on the process of amyloid-type protein aggregation. Amyloid fibrils are an important hallmark misfolding diseases and therefore have been investigated for decades. Only recently, however, atomic or near-atomic resolution structures elucidated from various in vitro ex vivo obtained fibrils. In parallel, fibril formation has studied under highly artificial but comparatively reproducible conditions. The starts with a summary what is known speculated aggregation experiments. A partially hypothetic selection model be described that may suitable to explain why amyloid look way they do, particular, at least all so far reported high cryo-electron microscopy register, cross-β-sheet mostly consist two protofilaments twisted around each other. An intrinsic feature prion-like nature assemblies. Transferring point view situation not straightforward, hypothetic, leaves many open questions need addressed future.

Language: Английский

Citations

153
Mechanisms and pathology of protein misfolding and aggregation DOI
Nikolaos Louros, Joost Schymkowitz, Frédéric Rousseau

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2023, Volume and Issue: 24(12), P. 912 - 933

Published: Sept. 8, 2023

Language: Английский

Citations

105
A central chaperone-like role for 14-3-3 proteins in human cells DOI Creative Commons
Dmitri Segal,

Stefan Maier,

Giovanni J. Mastromarco

et al.

Molecular Cell, Journal Year: 2023, Volume and Issue: 83(6), P. 974 - 993.e15

Published: March 1, 2023

Language: Английский

Citations

44
Misfolded protein oligomers: mechanisms of formation, cytotoxic effects, and pharmacological approaches against protein misfolding diseases DOI Creative Commons
Dillon J. Rinauro, Fabrizio Chiti, Michele Vendruscolo

et al.

Molecular Neurodegeneration, Journal Year: 2024, Volume and Issue: 19(1)

Published: Feb. 20, 2024

The conversion of native peptides and proteins into amyloid aggregates is a hallmark over 50 human disorders, including Alzheimer's Parkinson's diseases. Increasing evidence implicates misfolded protein oligomers produced during the formation process as primary cytotoxic agents in many these devastating conditions. In this review, we analyze processes by which are formed, their structures, physicochemical properties, population dynamics, mechanisms cytotoxicity. We then focus on drug discovery strategies that target ability to disrupt cell physiology trigger degenerative processes.

Language: Английский

Citations

43
Molecular structure and interactions within amyloid-like fibrils formed by a low-complexity protein sequence from FUS DOI Creative Commons
Myungwoon Lee, Ujjayini Ghosh, Kent R. Thurber

et al.

Nature Communications, Journal Year: 2020, Volume and Issue: 11(1)

Published: Nov. 12, 2020

Protein domains without the usual distribution of amino acids, called low complexity (LC) domains, can be prone to self-assembly into amyloid-like fibrils. Self-assembly LC that are nearly devoid hydrophobic residues, such as 214-residue domain RNA-binding protein FUS, is particularly intriguing from biophysical perspective and biomedically relevant due its occurrence within neurons in amyotrophic lateral sclerosis, frontotemporal dementia, other neurodegenerative diseases. We report a high-resolution molecular structural model for fibrils formed by C-terminal half FUS (FUS-LC-C, residues 111-214), based on density map with 2.62 Å resolution cryo-electron microscopy (cryo-EM). In FUS-LC-C fibril core, 112-150 adopt U-shaped conformations form two subunits in-register, parallel cross-β structures, arranged quasi-2

Language: Английский

Citations

94
Looking Beyond the Core: The Role of Flanking Regions in the Aggregation of Amyloidogenic Peptides and Proteins DOI Creative Commons
Sabine M. Ulamec, David J. Brockwell, Sheena E. Radford

et al.

Frontiers in Neuroscience, Journal Year: 2020, Volume and Issue: 14

Published: Dec. 1, 2020

Amyloid proteins are involved in many neurodegenerative disorders such as Alzheimer’s disease [Tau, β (Aβ)], Parkinson’s [alpha-synuclein (αSyn)], and amyotrophic lateral sclerosis (TDP-43). Driven by the early observation of presence ordered structure within amyloid fibrils potential to develop inhibitors their formation, a major goal field has been elucidate fold at atomic resolution. This now achieved for wide variety sequences using solid-state NMR, microcrystallography, X-ray fiber diffraction cryo-electron microscopy. These studies, together with silico methods able predict aggregation-prone regions (APRs) protein sequences, have provided wealth information about fibril cores that comprise fold. Structural kinetic analyses also shown amyloidogenic often contain less well-ordered outside core (termed here flanking regions) modulate function, toxicity and/or aggregation rates. regions, which form dynamically disordered “fuzzy coat” around core, play key parts physiological roles functional amyloids, including binding RNA phase separation. They mediators chaperone membrane binding/disruption toxic assemblies. Here, we review role different spanning both disease, context aggregation, cellular (dys)function. Understanding properties these could provide new opportunities target disease-related without disturbing critical biological functions.

Language: Английский

Citations

92
Fibril structures of diabetes-related amylin variants reveal a basis for surface-templated assembly DOI
Rodrigo Gallardo, M.G. Iadanza, Yong Xu

et al.

Nature Structural & Molecular Biology, Journal Year: 2020, Volume and Issue: 27(11), P. 1048 - 1056

Published: Sept. 14, 2020

Language: Английский

Citations

89
Two Decades of Studying Functional Amyloids in Microorganisms DOI
Shon A. Levkovich, Ehud Gazit, Dana Laor Bar‐Yosef

et al.

Trends in Microbiology, Journal Year: 2020, Volume and Issue: 29(3), P. 251 - 265

Published: Oct. 9, 2020

Language: Английский

Citations

88