A compositional view comparing modern biological condensates and primitive phase‐separated compartments DOI Creative Commons
Selene M. C. Cannelli, R. S. Gupta, Tan Dat Nguyen

et al.

Peptide Science, Journal Year: 2023, Volume and Issue: 115(6)

Published: Aug. 30, 2023

Abstract Liquid–liquid phase separation (LLPS) is a process that often occurs due to binding between oppositely charged biopolymers, and has gained increasing attention recently their ubiquity in biological systems ability direct essential cellular processes. However, while these discoveries biology are recent, the field of origins life been investigating LLPS for nearly 100 years, ever since first suggestions by Oparin Haldane primitive could have precursors cells on Earth. Since then, significant amount work done elucidate different relevant as protocellular models. Given structural similarities modern membraneless organelles, there may even be an evolutionary link two, although this remains question answered. Nevertheless, order answer this, source compares compositional aspects condensates necessary. Here, we focus organelles composed intrinsically disordered proteins (IDPs) nucleic acids. Then, parallel, explore compartments simple biopolymers such short peptides This followed discussion how biomolecules Earth originated, analyzing environmental chemical conditions favored Finally, directly compare composition phase‐separated compartments, further discussing potential IDPs early Earth, but also evolution from membrane‐bound cells. review aims provide comparison structures help researchers both fields understand current state knowledge, knowledge evolved, gaps need addressed.

Language: Английский

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
Coronavirus accessory protein ORF3 biology and its contribution to viral behavior and pathogenesis DOI Creative Commons
Fusheng Si, Shuai Song,

Ruisong Yu

et al.

iScience, Journal Year: 2023, Volume and Issue: 26(4), P. 106280 - 106280

Published: Feb. 28, 2023

Coronavirus porcine epidemic diarrhea virus (PEDV) is classified in the genus Alphacoronavirus, family Coronaviridae that encodes only accessory protein, ORF3 protein. However, how contributes to viral pathogenicity, adaptability, and replication obscure. In this review, we summarize current knowledge identify gaps many aspects of protein PEDV, with emphasis on its unique biological features, including membrane topology, Golgi retention mechanism, potential intrinsic disordered property, functional motifs, glycosylation, codon usage phenotypes related genetic evolution gene expression. addition, propose intriguing questions hope stimulate further studies encourage collaboration among virologists worldwide provide constructive about characteristics functions by which their role clarifying behavior pathogenesis can be possible.

Language: Английский

Citations

18
Intrinsic factors behind long COVID: IV. Hypothetical roles of the SARS‐CoV‐2 nucleocapsid protein and its liquid–liquid phase separation DOI

Ahmed Eltayeb,

Faisal Al‐Sarraj, Mona G. Alharbi

et al.

Journal of Cellular Biochemistry, Journal Year: 2024, Volume and Issue: 125(3)

Published: Feb. 13, 2024

Abstract When the SARS‐CoV‐2 virus infects humans, it leads to a condition called COVID‐19 that has wide spectrum of clinical manifestations, from no symptoms acute respiratory distress syndrome. The initiates damage by attaching ACE‐2 protein on surface endothelial cells line blood vessels and using these as hosts for replication. Reactive oxygen species levels are increased during viral replication, which oxidative stress. About three‐fifths (~60%) people who get infected with eradicate their body after 28 days recover normal activity. However, large fraction (~40%) suffer various (anosmia and/or ageusia, fatigue, cough, myalgia, cognitive impairment, insomnia, dyspnea, tachycardia) beyond 12 weeks diagnosed syndrome long COVID. Long‐term studies in group contracted have been contrasted noninfected matched people. A subset can be distinguished set cytokine markers persistent, low‐grade inflammation often self‐report two or more bothersome symptoms. No medication alleviate efficiently. Coronavirus nucleocapsid proteins investigated extensively potential drug targets due key roles among is ability bind respective genomic RNAs incorporation into emerging virions. This review highlights basic its undergo liquid–liquid phase separation. We hypothesize this separation may contribute hypothesis unlocks new investigation angles could potentially open novel avenues better understanding COVID treating condition.

Language: Английский

Citations

6
Flexibility of the Rotavirus NSP2 C-Terminal Region Supports Factory Formation via Liquid-Liquid Phase Separation DOI

Sarah L. Nichols,

Emil M. Nilsson,

Heather M. Brown

et al.

Journal of Virology, Journal Year: 2023, Volume and Issue: 97(2)

Published: Feb. 7, 2023

Viruses often condense the materials needed for their replication into discrete intracellular factories. For rotaviruses, agents of severe gastroenteritis in children, factory formation is mediated part by an octameric protein called NSP2.

Language: Английский

Citations

14
Structure, function and immune evasion strategies of aquareoviruses, with focus on grass carp reovirus DOI
Peng Wei Li, Jie Zhang, Ming Xian Chang

et al.

Reviews in Aquaculture, Journal Year: 2023, Volume and Issue: 16(1), P. 410 - 432

Published: July 4, 2023

Abstract Aquareoviruses (AqRVs) can infect various wild or cultured bony fishes with serious muscle and viscera haemorrhage syndrome have caused severe economic losses worldwide. Accumulating evidences revealed the functions of viral proteins AqRVs in RNA transcription, virion assembly, cell attachment and/or replication. In addition, structural information transcription mechanism been in‐depth studied through cryo‐electron microscopy combined three‐dimensional image reconstruction. Although far from enough, functional studies provide substantial insights into how coordinate replication escape host immune response. Grass carp reovirus (GCRV) is most pathogenic AqRV isolated aquatic animals. The completion GCRV lifecycle requires participation proteins. So far, many factors involved entry identified. Based on function lifecycle, vaccines antiviral agents developed to prevent infection GCRV. This review summarises characteristics composition core AqRVs, as well synergistic mechanisms genome virus AqRVs. highlights our current knowledge for replication, non‐structural proteins, mechanisms, especially A better understanding structure, evasion strategies will offer new targets prevention control aquaculture.

Language: Английский

Citations

14
Buffer choice and pH strongly influence phase separation of SARS-CoV-2 nucleocapsid with RNA DOI
Nina C. Kathe, Mihajlo Novakovic, Frédéric H.‐T. Allain

et al.

Molecular Biology of the Cell, Journal Year: 2024, Volume and Issue: 35(5)

Published: April 3, 2024

The SARS-CoV-2 nucleocapsid (N) protein is crucial for virus replication and genome packaging. N forms biomolecular condensates both in vitro vivo a process known as liquid–liquid phase separation (LLPS), but the exact factors regulating LLPS of are not fully understood. Here, we show that pH buffer choice have profound impact on protein. degree highly dependent solution, which correlated with histidine protonation Specifically, demonstrate H356 essential phosphate buffer. Moreover, electrostatic interactions molecules specific amino acid residues able to alter net charge protein, thus influencing its ability undergo presence RNA. Overall, these findings reveal even subtle changes or surface caused by system can strongly influence behavior, point main driving forces separation. Further, our emphasize importance experimental parameters when studying biomolecules, especially context viral infections where intracellular milieu undergoes drastic normally decreases.

Language: Английский

Citations

5
Viral amyloids: New opportunities for antiviral therapeutic strategies DOI Creative Commons
Frank Gondelaud, Pierre‐Yves Lozach, Sonia Longhi

et al.

Current Opinion in Structural Biology, Journal Year: 2023, Volume and Issue: 83, P. 102706 - 102706

Published: Sept. 30, 2023

Language: Английский

Citations

10
14‐3‐3 Family of Proteins: Biological Implications, Molecular Interactions, and Potential Intervention in Cancer, Virus and Neurodegeneration Disorders DOI Creative Commons
Zheng Yao Low, Ashley Jia Wen Yip, Alvin Man Lung Chan

et al.

Journal of Cellular Biochemistry, Journal Year: 2024, Volume and Issue: 125(7)

Published: June 30, 2024

ABSTRACT The 14‐3‐3 family of proteins are highly conserved acidic eukaryotic (25–32 kDa) abundantly present in the body. Through numerous binding partners, is responsible for many essential cellular pathways, such as cell cycle regulation and gene transcription control. Hence, its dysregulation has been linked to onset critical illnesses cancers, neurodegenerative diseases viral infections. Interestingly, explorative studies have revealed an inverse correlation protein cancer diseases, direct manipulation by virus enhance infection capacity dramatically extended significance. Of these, COVID‐19 interference SARS‐CoV‐2 nucleocapsid (N) during virion assembly. Given predisposition towards multiple host signalling it vital understand holistic interactions between unravel potential therapeutic unit future. As such, general structure properties proteins, well their known biological functions implications cancer, neurodegeneration, viruses, were covered this review. Furthermore, target associated was discussed.

Language: Английский

Citations

3
An Overview of Liquid-Liquid Phase Separation and Its Mechanisms in Sepsis DOI Creative Commons
Meiling Cao, Xinyi Zhang, Xiaohan Wang

et al.

Journal of Inflammation Research, Journal Year: 2025, Volume and Issue: Volume 18, P. 3969 - 3980

Published: March 1, 2025

Sepsis is a systemic inflammatory response syndrome triggered by the invasion of bacteria or pathogenic microorganisms into human body, which may lead to variety serious complications and pose threat patient's life health. Liquid-liquid phase separation (LLPS) biomolecular process in different biomolecules, such as proteins nucleic acids, form liquid condensates through interactions, these play key roles cellular physiological processes. LLPS affect development sepsis several pathways, modulation factors, immune responses, cell death, altering function activity which, turn, infection inflammation. In this paper, we first discuss mechanism separation, then summarize studies sepsis, finally propose potential application treatment strategies, while pointing out limitations existing directions for future research.

Language: Английский

Citations

0
Liquid–liquid phase separation of LARP7 restrains HIV-1 replication DOI Creative Commons
Zhuoxin Li, Xiya Fang, Bing Zhao

et al.

EMBO Reports, Journal Year: 2025, Volume and Issue: unknown

Published: March 20, 2025

Abstract HIV-1 initiates replication by its transactivator Tat, hijacking the positive transcription elongation factor b (P-TEFb) in host cell. Most P-TEFb is maintained an inactive state 7SK snRNP until it brought to initiation complex cellular or viral transactivators that accelerate and facilitate production of full-length transcripts. Here, we report infection triggers liquid-liquid phase separation LARP7, a central component snRNP. Tat incorporated into HIV-1-induced LARP7 condensates after infection. Conserved lysine residues intrinsically disordered region are essential for both inhibition Tat-mediated transcription. These findings identify mechanism wherein sequestered within condensates, restraining

Language: Английский

Citations

0