Sequence-Dependent Conformational Transitions of Disordered Proteins During Condensation DOI Creative Commons
Jiahui Wang, Dinesh Sundaravadivelu Devarajan,

Young C. Kim

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Jan. 12, 2024

Intrinsically disordered proteins (IDPs) can form biomolecular condensates through phase separation. It is recognized that the conformation of IDPs in dense and dilute phases as well at interfaces critically impact resulting properties associated with their functionality. However, a comprehensive understanding conformational transitions during condensation remains elusive. In this study, we employ coarse-grained polyampholyte model, comprising an equal number oppositely charged residues-glutamic acid lysine-whereby conformations behavior be readily tuned by altering protein sequence. By manipulating sequence patterns from perfectly alternating to block-like, obtain chains ideal-like semi-compact structures phase, while chain approximately ideal chain, irrespective performing simulations different concentrations, find assemble small oligomeric clusters accompanied gradual swelling individual chains. We further demonstrate these findings are applicable several naturally occurring involved formation biological condensates. Concurrently, delve deeper into within condensate, revealing interface show strong dependence, but remain more collapsed than those bulk-like phase. This study addresses critical gaps our knowledge IDP function

Language: Английский

Amyloid formation as a protein phase transition DOI
Thomas C. T. Michaels, Daoyuan Qian, Anđela Šarić

et al.

Nature Reviews Physics, Journal Year: 2023, Volume and Issue: 5(7), P. 379 - 397

Published: June 27, 2023

Language: Английский

Citations

81
The interface of condensates of the hnRNPA1 low-complexity domain promotes formation of amyloid fibrils DOI Creative Commons

Miriam Linsenmeier,

Lenka Faltova,

Chiara Morelli

et al.

Nature Chemistry, Journal Year: 2023, Volume and Issue: 15(10), P. 1340 - 1349

Published: Sept. 25, 2023

The maturation of liquid-like protein condensates into amyloid fibrils has been associated with several neurodegenerative diseases. However, the molecular mechanisms underlying this liquid-to-solid transition have remained largely unclear. Here we analyse formation mediated by condensation low-complexity domain hnRNPA1, a involved in amyotrophic lateral sclerosis. We show that phase separation and fibrillization are connected but distinct processes modulated different regions sequence. By monitoring spatial temporal evolution demonstrate does not occur homogeneously inside droplets is promoted at interface condensates. further coating surfactant molecules inhibits fibril formation. Our results reveal biomolecular hnRNPA1 promotes formation, therefore suggesting interfaces as potential novel therapeutic target against aberrant amyloids condensation.

Language: Английский

Citations

79
Mass photometric detection and quantification of nanoscale α-synuclein phase separation DOI
Soumik Ray, Thomas O. Mason, Lars Boyens‐Thiele

et al.

Nature Chemistry, Journal Year: 2023, Volume and Issue: 15(9), P. 1306 - 1316

Published: June 19, 2023

Language: Английский

Citations

68
Coacervate Droplets for Synthetic Cells DOI Creative Commons

Zi Lin,

Thomas Beneyton, Jean‐Christophe Baret

et al.

Small Methods, Journal Year: 2023, Volume and Issue: 7(12)

Published: July 18, 2023

Abstract The design and construction of synthetic cells – human‐made microcompartments that mimic features living have experienced a real boom in the past decade. While many efforts been geared toward assembling membrane‐bounded compartments, coacervate droplets produced by liquid–liquid phase separation emerged as an alternative membrane‐free compartmentalization paradigm. Here, dual role cell research is discussed: encapsulated within membrane‐enclosed coacervates act surrogates membraneless organelles ubiquitously found cells; alternatively, they can be viewed crowded cytosol‐like chassis for constructing integrated cells. After introducing key concepts coacervation illustrating chemical diversity systems, their physicochemical properties resulting bioinspired functions are emphasized. Moving from suspensions free floating coacervates, two nascent roles these highlighted: organelle‐like modules templates. Building discussion on recent studies literature, potential to assemble capable multiple life‐inspired showcased. Future challenges still tackled field finally discussed.

Language: Английский

Citations

52
Open questions on liquid–liquid phase separation DOI Creative Commons
Evan Spruijt

Communications Chemistry, Journal Year: 2023, Volume and Issue: 6(1)

Published: Feb. 3, 2023

Liquid-liquid phase separation (LLPS) underlies the formation of intracellular membraneless compartments in biology and may have played a role protocells that concentrate key chemicals during origins life. While LLPS simple systems, such as oil water, is well understood, many aspects complex, out-of-equilibrium molecular systems remain elusive. Here, author discusses open questions recent insights related to formation, function fate condensates both cell protocell research.

Language: Английский

Citations

43
Molecular Crowding: The History and Development of a Scientific Paradigm DOI Creative Commons
Caterina Alfano, Yann Fichou, Klaus Huber

et al.

Chemical Reviews, Journal Year: 2024, Volume and Issue: 124(6), P. 3186 - 3219

Published: March 11, 2024

It is now generally accepted that macromolecules do not act in isolation but "live" a crowded environment, is, an environment populated by numerous different molecules. The field of molecular crowding has its origins the far 80s became only end 90s. In present issue, we discuss various aspects are influenced and need to consider effects. This Review meant as introduction theme analysis evolution concept through time from colloidal polymer physics more biological perspective. We introduce themes will be thoroughly treated other Reviews issue. our intentions, each may stand itself, complete collection aspiration provide complementary perspectives propose holistic view crowding.

Language: Английский

Citations

37
Macromolecular Crowding, Phase Separation, and Homeostasis in the Orchestration of Bacterial Cellular Functions DOI Creative Commons
Begoña Monterroso, William Margolin, Arnold J. Boersma

et al.

Chemical Reviews, Journal Year: 2024, Volume and Issue: 124(4), P. 1899 - 1949

Published: Feb. 8, 2024

Macromolecular crowding affects the activity of proteins and functional macromolecular complexes in all cells, including bacteria. Crowding, together with physicochemical parameters such as pH, ionic strength, energy status, influences structure cytoplasm thereby indirectly function. Notably, also promotes formation biomolecular condensates by phase separation, initially identified eukaryotic cells but more recently discovered to play key functions Bacterial require a variety mechanisms maintain homeostasis, particular environments fluctuating conditions, is emerging one mechanism. In this work, we connect homeostasis function bacterial cell compare supramolecular structures found bacteria those cells. We focus on effects separation control chromosome replication, segregation, division, discuss contribution fitness adaptation environmental stress.

Language: Английский

Citations

31
A solid beta-sheet structure is formed at the surface of FUS droplets during aging DOI Creative Commons
Leonidas Emmanouilidis, Ettore Bartalucci,

Yelena Kan

et al.

Nature Chemical Biology, Journal Year: 2024, Volume and Issue: 20(8), P. 1044 - 1052

Published: March 11, 2024

Abstract Phase transitions are important to understand cell dynamics, and the maturation of liquid droplets is relevant neurodegenerative disorders. We combined NMR Raman spectroscopies with microscopy follow, over a period days months, droplet protein fused in sarcoma (FUS). Our study reveals that surface plays critical role this process, while RNA binding prevents it. The kinetics faster an agarose-stabilized biphasic sample compared monophasic condensed sample, owing larger surface-to-volume ratio. In addition, spectroscopy reports structural differences upon between inside droplets, which comprised β-sheet content, as revealed by solid-state NMR. agreement these observations, solid crust-like shell observed at using microaspiration. Ultimately, matured were converted into fibrils involving prion-like domain well first RGG motif.

Language: Английский

Citations

28
Protein misfolding and amyloid nucleation through liquid–liquid phase separation DOI
S. Mukherjee, Manisha Poudyal, K. Dave

et al.

Chemical Society Reviews, Journal Year: 2024, Volume and Issue: 53(10), P. 4976 - 5013

Published: Jan. 1, 2024

Protein misfolding and amyloid aggregation, linked to neurodegenerative diseases, can result from liquid–liquid phase separation (LLPS) a subsequent liquid-to-solid transition. This represents LLPS as generic mechanism in nucleation.

Language: Английский

Citations

25
The role of biomolecular condensates in protein aggregation DOI
Brent S. Visser, Wojciech P. Lipiński, Evan Spruijt

et al.

Nature Reviews Chemistry, Journal Year: 2024, Volume and Issue: 8(9), P. 686 - 700

Published: Aug. 12, 2024

Language: Английский

Citations

23