Protein Condensates and Protein Aggregates: In Vitro, in the Cell, and In Silico DOI Creative Commons
Katja Venko, Eva Žerovnik

Frontiers in Bioscience-Landmark, Journal Year: 2023, Volume and Issue: 28(8), P. 183 - 183

Published: Aug. 28, 2023

Similar to other polypeptides and electrolytes, proteins undergo phase transitions, obeying physicochemical laws. They can liquid-to-gel liquid-to-liquid transitions. Intrinsically disordered are particularly susceptible separation. After a general introduction, the principles of in vitro studies protein folding, aggregation, condensation described. Numerous recent older have confirmed that process liquid-liquid separation (LLPS) leads various condensed bodies cells, which is one way cells manage stress. We review what known about aggregation cell, notwithstanding protective pathological roles aggregates. This includes membrane-less organelles cytotoxicity prefibrillar oligomers amyloid-forming proteins. then describe evaluate bioinformatic (in silico) methods for predicting aggregation-prone regions form amyloids, prions, condensates.

Language: Английский

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
Evidence for widespread cytoplasmic structuring into mesoscale condensates DOI
Felix C. Keber, Thao Nguyen, Andrea Mariossi

et al.

Nature Cell Biology, Journal Year: 2024, Volume and Issue: 26(3), P. 346 - 352

Published: Feb. 29, 2024

Language: Английский

Citations

34
Transcriptional condensates: a blessing or a curse for gene regulation? DOI Creative Commons

Martín Stortz,

Diego M. Presman, Valeria Levi

et al.

Communications Biology, Journal Year: 2024, Volume and Issue: 7(1)

Published: Feb. 16, 2024

Whether phase-separation is involved in the organization of transcriptional machinery and if it aids or inhibits process a matter intense debate. In this Mini Review, we will cover current knowledge regarding role condensates on gene expression regulation. We summarize latest discoveries relationship between condensate formation, genome organization, activity, focusing strengths weaknesses experimental approaches used to interrogate these aspects transcription living cells. Finally, discuss challenges for future research.

Language: Английский

Citations

26
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
MolPhase, an advanced prediction algorithm for protein phase separation DOI Creative Commons
Qiyu Liang, Nana Peng, Yi Xie

et al.

The EMBO Journal, Journal Year: 2024, Volume and Issue: 43(9), P. 1898 - 1918

Published: April 2, 2024

Abstract We introduce MolPhase, an advanced algorithm for predicting protein phase separation (PS) behavior that improves accuracy and reliability by utilizing diverse physicochemical features extensive experimental datasets. MolPhase applies a user-friendly interface to compare distinct biophysical side-by-side along sequences. By additional comparison with structural predictions, enables efficient predictions of new phase-separating proteins guides hypothesis generation design. Key contributing factors underlying include electrostatic pi-interactions, disorder, prion-like domains. As example, finds phytobacterial type III effectors (T3Es) are highly prone homotypic PS, which was experimentally validated in vitro biochemically vivo plants, mimicking their injection accumulation the host during microbial infection. The characteristics T3Es dictate patterns association multivalent interactions, influencing material properties droplets based on surrounding microenvironment or vitro. Robust integration MolPhase’s effective prediction validation exhibit potential evaluate explore how biomolecule PS functions biological systems.

Language: Английский

Citations

18
Label-Free Techniques for Probing Biomolecular Condensates DOI
Khalid A. Ibrahim,

Akhil S. Naidu,

Helena Miljkovic

et al.

ACS Nano, Journal Year: 2024, Volume and Issue: 18(16), P. 10738 - 10757

Published: April 12, 2024

Biomolecular condensates play important roles in a wide array of fundamental biological processes, such as cellular compartmentalization, regulation, and other biochemical reactions. Since their discovery first observations, an extensive expansive library tools has been developed to investigate various aspects properties, encompassing structural compositional information, material evolution throughout the life cycle from formation eventual dissolution. This Review presents overview expanded set methods that researchers use probe properties biomolecular across diverse scales length, concentration, stiffness, time. In particular, we review recent years' exciting development label-free techniques methodologies. We broadly organize into 3 categories: (1) imaging-based techniques, transmitted-light microscopy (TLM) Brillouin (BM), (2) force spectroscopy atomic (AFM) optical tweezer (OT), (3) microfluidic platforms emerging technologies. point out tools' key opportunities, challenges, future perspectives analyze correlative potential well compatibility with techniques. Additionally, namely, differential dynamic (DDM) interferometric scattering (iSCAT), have huge for applications studying condensates. Finally, highlight how some these can be translated diagnostics therapy purposes. hope this serves useful guide new field aids advancing biophysical study

Language: Английский

Citations

11
Unlocking the electrochemical functions of biomolecular condensates DOI
Yifan Dai, Zhen‐Gang Wang, Richard N. Zare

et al.

Nature Chemical Biology, Journal Year: 2024, Volume and Issue: 20(11), P. 1420 - 1433

Published: Sept. 26, 2024

Language: Английский

Citations

10
Defining basic rules for hardening influenza A virus liquid condensates DOI Creative Commons
Temitope Akhigbe Etibor, Sílvia Vale-Costa, Sindhuja Sridharan

et al.

eLife, Journal Year: 2023, Volume and Issue: 12

Published: April 4, 2023

In biological systems, liquid and solid-like biomolecular condensates may contain the same molecules but their behaviour, including movement, elasticity, viscosity, is different on account of distinct physicochemical properties. As such, it known that phase transitions affect function material properties can be tuned by several factors temperature, concentration, valency. It is, however, unclear if some are more efficient than others at regulating behaviour. Viral infections good systems to address this question as they form de novo part replication programmes. Here, we used influenza A virus (IAV) cytosolic condensates, AKA viral inclusions, provide a proof concept condensate hardening via changes in valency its components altering concentration or temperature cell. Liquid IAV inclusions hardened targeting vRNP (viral ribonucleoprotein) interactions NP (nucleoprotein) oligomerising molecule, nucleozin, both vitro vivo without affecting host proteome abundance nor solubility. This study starting point for understanding how pharmacologically modulate offer opportunities alternative antiviral strategies.

Language: Английский

Citations

22
Condensate interfaces can accelerate protein aggregation DOI Creative Commons

Chang-Hyun Choi,

Daniel S.W. Lee, David W. Sanders

et al.

Biophysical Journal, Journal Year: 2023, Volume and Issue: 123(11), P. 1404 - 1413

Published: Oct. 13, 2023

Protein aggregates, formed from the assembly of aberrant, misfolded proteins, are a hallmark neurodegenerative diseases. Disease-associated aggregates such as mutant Huntingtin polyQ inclusions, typically enriched in p62/SQSTM1, an oligomeric protein that binds to and sequesters aberrant proteins. p62 has been suggested sequester proteins through formation liquid-like biomolecular condensates, but physical mechanisms by which condensates may regulate pathological aggregation remain unclear. Here, we use light-inducible biomimetic condensate system show enhance coarsening PolyQ interface-mediated sequestration, accelerates accumulation into larger aggregates. However, resulting large accumulate polyubiquitinated depletes free p62, ultimately suppressing further condensation. This dynamic interplay between solid downstream consequences on phase behavior associated regulatory could contribute onset progression

Language: Английский

Citations

20
Emerging experimental methods to study the thermodynamics of biomolecular condensate formation DOI Creative Commons
Soumik Ray, Alexander K. Buell

The Journal of Chemical Physics, Journal Year: 2024, Volume and Issue: 160(9)

Published: March 6, 2024

The formation of biomolecular condensates in vivo is increasingly recognized to underlie a multitude crucial cellular functions. Furthermore, the evolution highly dynamic protein into progressively less reversible assemblies thought be involved variety disorders, from cancer over neurodegeneration rare genetic disorders. There an increasing need for efficient experimental methods characterize thermodynamics condensate and that can used screening campaigns identify rationally design modifying compounds. Theoretical advances field are also identifying key parameters measured order obtain comprehensive understanding underlying interactions driving forces. Here, we review recent progress development quantitative study forces behind temporal condensates.

Language: Английский

Citations

8