Liquid–liquid phase separation of tau: From molecular biophysics to physiology and disease DOI Creative Commons

K. Sandeep,

Adriana Savastano, Priyanka Singh

et al.

Protein Science, Journal Year: 2021, Volume and Issue: 30(7), P. 1294 - 1314

Published: April 30, 2021

Biomolecular condensation via liquid-liquid phase separation (LLPS) of intrinsically disordered proteins/regions (IDPs/IDRs), with and without nucleic acids, has drawn widespread interest due to the rapidly unfolding role phase-separated condensates in a diverse range cellular functions human diseases. form transient multivalent intermolecular forces that sequester proteins acids into liquid-like membrane-less compartments. However, aberrant transitions gel-like or solid-like aggregates might play an important neurodegenerative other Tau, microtubule-associated neuronal IDP, is involved microtubule stabilization, regulates axonal outgrowth transport neurons. A growing body evidence indicates tau can accomplish some its activities LLPS. liquid-to-solid transition resulting abnormal aggregation associated The physical chemistry crucial for governing propensity biomolecular which governed by various intramolecular interactions leading simple one-component complex multi-component condensates. In this review, we aim at capturing current scientific state unveiling intriguing molecular mechanism tau. We particularly focus on amalgamation existing emerging biophysical tools offer unique spatiotemporal resolutions wide length- time-scales. also discuss link between quantitative measurements novel biological insights believe account will provide broad multidisciplinary view association physiology disease.

Language: Английский

Modulation of cellular processes by histone and non-histone protein acetylation DOI
Maria Shvedunova, Asifa Akhtar

Nature Reviews Molecular Cell Biology, Journal Year: 2022, Volume and Issue: 23(5), P. 329 - 349

Published: Jan. 18, 2022

Language: Английский

Citations

519
A conceptual framework for understanding phase separation and addressing open questions and challenges DOI Creative Commons
Tanja Mittag, Rohit V. Pappu

Molecular Cell, Journal Year: 2022, Volume and Issue: 82(12), P. 2201 - 2214

Published: June 1, 2022

Language: Английский

Citations

493
Deciphering how naturally occurring sequence features impact the phase behaviours of disordered prion-like domains DOI
Anne Bremer, Mina Farag, Wade M. Borcherds

et al.

Nature Chemistry, Journal Year: 2021, Volume and Issue: 14(2), P. 196 - 207

Published: Dec. 20, 2021

Language: Английский

Citations

398
The molecular basis for cellular function of intrinsically disordered protein regions DOI
Alex S. Holehouse, Birthe B. Kragelund

Nature Reviews Molecular Cell Biology, Journal Year: 2023, Volume and Issue: 25(3), P. 187 - 211

Published: Nov. 13, 2023

Language: Английский

Citations

235
Phase Transitions of Associative Biomacromolecules DOI
Rohit V. Pappu, Samuel R. Cohen, Furqan Dar

et al.

Chemical Reviews, Journal Year: 2023, Volume and Issue: 123(14), P. 8945 - 8987

Published: March 7, 2023

Multivalent proteins and nucleic acids, collectively referred to as multivalent associative biomacromolecules, provide the driving forces for formation compositional regulation of biomolecular condensates. Here, we review key concepts phase transitions aqueous solutions specifically that include folded domains intrinsically disordered regions. The these systems come under rubric coupled segregative transitions. underlying processes are presented, their relevance condensates is discussed.

Language: Английский

Citations

229
A prion-like protein regulator of seed germination undergoes hydration-dependent phase separation DOI Creative Commons
Yanniv Dorone, Steven Boeynaems, Eduardo Flores

et al.

Cell, Journal Year: 2021, Volume and Issue: 184(16), P. 4284 - 4298.e27

Published: July 6, 2021

Language: Английский

Citations

148
Systematic identification of conditionally folded intrinsically disordered regions by AlphaFold2 DOI Creative Commons
T. Reid Alderson, Iva Pritišanac, Đesika Kolarić

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2023, Volume and Issue: 120(44)

Published: Oct. 25, 2023

The AlphaFold Protein Structure Database contains predicted structures for millions of proteins. For the majority human proteins that contain intrinsically disordered regions (IDRs), which do not adopt a stable structure, it is generally assumed these have low AlphaFold2 confidence scores reflect low-confidence structural predictions. Here, we show assigns confident to nearly 15% IDRs. By comparison experimental NMR data subset IDRs are known conditionally fold (i.e., upon binding or under other specific conditions), find often predicts structure folded state. Based on databases fold, estimate can identify folding at precision as high 88% 10% false positive rate, remarkable considering IDR were minimally represented in its training data. We disease mutations fivefold enriched over general and up 80% prokaryotes compared less than 20% eukaryotic These results indicate large proteomes eukaryotes function absence conditional folding, but acquire folds more sensitive mutations. emphasize predictions reveal functionally relevant plasticity within cannot offer realistic ensemble representations

Language: Английский

Citations

117
Design principles for creating synthetic underwater adhesives DOI
Amal Narayanan, Ali Dhinojwala, Abraham Joy

et al.

Chemical Society Reviews, Journal Year: 2021, Volume and Issue: 50(23), P. 13321 - 13345

Published: Jan. 1, 2021

Water prevents adhesion by disrupting the interfacial interactions and weakening cohesive network of adhesive. This review summarizes recent developments in physical chemical design principles underwater adhesives.

Language: Английский

Citations

110
RNA m6A regulates transcription via DNA demethylation and chromatin accessibility DOI
Shuang Deng, Jialiang Zhang, Jiachun Su

et al.

Nature Genetics, Journal Year: 2022, Volume and Issue: 54(9), P. 1427 - 1437

Published: Sept. 1, 2022

Language: Английский

Citations

102
The material properties of a bacterial-derived biomolecular condensate tune biological function in natural and synthetic systems DOI Creative Commons
Keren Lasker, Steven Boeynaems,

Vinson Lam

et al.

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Sept. 26, 2022

Intracellular phase separation is emerging as a universal principle for organizing biochemical reactions in time and space. It remains incompletely resolved how biological function encoded these assemblies whether this depends on their material state. The conserved intrinsically disordered protein PopZ forms condensates at the poles of bacterium Caulobacter crescentus, which turn orchestrate cell-cycle regulating signaling cascades. Here we show that properties are determined by balance between attractive repulsive forces mediated helical oligomerization domain an expanded region, respectively. A series mutants disrupting results span spectrum, from liquid to solid. narrow range condensate supports proper cell division, linking emergent organismal fitness. We use insights repurpose modular platform generating tunable synthetic human cells.

Language: Английский

Citations

86