DNA‐dependent phase separation by human SSB2 (NABP1/OBFC2A) protein points to adaptations to eukaryotic genome repair processes DOI Creative Commons
Zoltán J. Kovács, Gábor M. Harami, János Pálinkás

et al.

Protein Science, Journal Year: 2024, Volume and Issue: 33(4)

Published: March 21, 2024

Single-stranded DNA binding proteins (SSBs) are ubiquitous across all domains of life and play essential roles via stabilizing protecting single-stranded (ss) as well organizing multiprotein complexes during replication, recombination, repair. Two mammalian SSB paralogs (hSSB1 hSSB2 in humans) were recently identified shown to be involved various genome maintenance processes. Following our recent discovery the liquid-liquid phase separation (LLPS) propensity Escherichia coli (Ec) SSB, here we show that also forms LLPS condensates under physiologically relevant ionic conditions. Similar seen for EcSSB, demonstrate contribution hSSB2's C-terminal intrinsically disordered region (IDR) condensate formation, selective enrichment metabolic condensates. However, contrast EcSSB-driven is inhibited by ssDNA binding, requires nucleic acid especially facilitated ssDNA. Our results reveal an evolutionarily conserved role SSB-mediated spatiotemporal organization complexes. At same time, differential features EcSSB point functional adaptations prokaryotic versus eukaryotic contexts.

Language: Английский

Hydrophilic polymers: Current trends and visions for the future DOI Creative Commons

Niamh Bayliss,

Bernhard V. K. J. Schmidt

Progress in Polymer Science, Journal Year: 2023, Volume and Issue: 147, P. 101753 - 101753

Published: Oct. 18, 2023

Hydrophilic polymers are a major class of in polymer science. They found broad range applications from superabsorbers to drug-delivery. In recent years, plethora impactful developments hydrophilic have been reported. The present review gives an overview over these with focus on frequently studied types, aqueous multi-phase systems, block copolymer self-assembly and particles. We cover fundamental work concepts but also high relevance for application. Finally, we give outlook towards current challenges future the field. further development is great importance will significant impact biomedicine every-day life.

Language: Английский

Citations

37
A viral biomolecular condensate coordinates assembly of progeny particles DOI
Matthew Charman, Nicholas Grams,

Namrata Kumar

et al.

Nature, Journal Year: 2023, Volume and Issue: 616(7956), P. 332 - 338

Published: April 5, 2023

Language: Английский

Citations

31
Rational design of phytovirucide inhibiting nucleocapsid protein aggregation in tomato spotted wilt virus DOI Creative Commons
Ningning Zan, Jiao Li, Jiahui Yao

et al.

Nature Communications, Journal Year: 2025, Volume and Issue: 16(1)

Published: Feb. 27, 2025

Ineffectiveness of managing plant viruses by chemicals has posed serious challenges in crop production. Recently, phase separation shown to play a key role viral lifecycle. Using inhibitors that can disturb biomolecular condensates formed for virus control been reported medical field. However, the applicability this promising antiviral tactic protection not explored. Here, we report an inhibitor, Z9, targets tomato spotted wilt (TSWV) N protein. Z9 is capable interacting with amino acids nucleic acid binding region TSWV N, disrupting assembly and RNA into phase-separated condensates, reduction which detrimental stability This study provides strategy separation-based control. Biomolecular have recognized as crucial process life cycle. authors inhibitor targeting nucleocapsid protein (N) disrupt its potential

Language: Английский

Citations

1
Liquid-liquid phase separation of nucleocapsid proteins during SARS-CoV-2 and HIV-1 replication DOI Creative Commons

Bao-An Chau,

Venessa Chen,

Alan Cochrane

et al.

Cell Reports, Journal Year: 2022, Volume and Issue: 42(1), P. 111968 - 111968

Published: Dec. 26, 2022

The leap of retroviruses and coronaviruses from animal hosts to humans has led two ongoing pandemics tens millions deaths worldwide. Retrovirus coronavirus nucleocapsid proteins have been studied extensively as potential drug targets due their central roles in virus replication, among which is capacity bind respective genomic RNAs for packaging into nascent virions. This review focuses on fundamental studies these how intrinsic abilities condense through liquid-liquid phase separation (LLPS) contribute viral replication. Therapeutic targeting condensates methodological advances are also described address future questions contributes

Language: Английский

Citations

34
Biomolecular condensates: insights into early and late steps of the HIV-1 replication cycle DOI Creative Commons
Francesca Di Nunzio, Vladimir N. Uversky, Andrew J. Mouland

et al.

Retrovirology, Journal Year: 2023, Volume and Issue: 20(1)

Published: April 7, 2023

Abstract A rapidly evolving understanding of phase separation in the biological and physical sciences has led to redefining virus-engineered replication compartments many viruses with RNA genomes. Condensation viral, host genomic subgenomic RNAs can take place evade innate immunity response help viral replication. Divergent prompt liquid–liquid (LLPS) invade cell. During HIV there are several steps involving LLPS. In this review, we characterize ability individual partners that assemble into biomolecular condensates (BMCs). Of note, bioinformatic analyses predict models line published observations. Importantly, BMCs contribute function key retroviral For example, reverse transcription takes within nuclear BMCs, called HIV-MLOs while during late steps, nucleocapsid acts as a driver or scaffold recruit client components aid assembly progeny virions. Overall, LLPS infections represents newly described event now appreciated virology field, also be considered an alternative pharmacological target current drug therapies especially when become resistant antiviral treatment.

Language: Английский

Citations

21
Liquid-liquid phase separation in DNA double-strand breaks repair DOI Creative Commons
Yunlong Wang, Wan-Wen Zhao,

Jie Shi

et al.

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(11)

Published: Nov. 15, 2023

Abstract DNA double-strand breaks (DSBs) are the fatal type of damage mostly induced by exposure genome to ionizing radiation or genotoxic chemicals. DSBs mainly repaired homologous recombination (HR) and nonhomologous end joining (NHEJ). To repair DSBs, a large amount factors was observed be concentrated at in specific spatiotemporal manner form center. Recently, this center characterized as condensate derived from liquid-liquid phase separation (LLPS) key factors. LLPS has been found mechanism membraneless organelles formation plays roles variety biological processes. In review, recent advances mechanisms repair-related condensates summarized.

Language: Английский

Citations

20
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
HIV-1 usurps mixed-charge domain-dependent CPSF6 phase separation for higher-order capsid binding, nuclear entry and viral DNA integration DOI Creative Commons
Sooin Jang, Gregory J. Bedwell, Satya P. Singh

et al.

Nucleic Acids Research, Journal Year: 2024, Volume and Issue: unknown

Published: Aug. 25, 2024

Abstract HIV-1 integration favors nuclear speckle (NS)-proximal chromatin and viral infection induces the formation of capsid-dependent CPSF6 condensates that colocalize with speckles (NSs). Although displays liquid-liquid phase separation (LLPS) activity in vitro, contributions its different intrinsically disordered regions, which includes a central prion-like domain (PrLD) capsid binding FG motif C-terminal mixed-charge (MCD), to LLPS remain unclear. Herein, we determined PrLD MCD both contribute vitro. Akin mutant CPSF6, cells expressing MCD-deleted uncharacteristically arrested at rim. While heterologous MCDs effectively substituted for function during infection, Arg-Ser domains from related SR proteins were largely ineffective. wildtype displayed similar affinities, imparted LLPS-dependent higher-order co-aggregation capsids vitro cellulo. NS depletion reduced puncta without significantly affecting into NS-proximal chromatin, appending onto protein partially restored virus penetration targeting knockout cells. We conclude MCD-dependent condensation underlies post-nuclear incursion DNA pathogenesis.

Language: Английский

Citations

8
Phase Separation: The Robust Modulator of Innate Antiviral Signaling and SARS-CoV-2 Infection DOI Creative Commons
Yi Zheng, Chengjiang Gao

Pathogens, Journal Year: 2023, Volume and Issue: 12(2), P. 243 - 243

Published: Feb. 3, 2023

SARS-CoV-2 has been a pandemic threat to human health and the worldwide economy, but efficient treatments are still lacking. Type I III interferons essential for controlling viral infection, indicating that antiviral innate immune signaling is critical defense against infection. Phase separation, one of basic molecular processes, governs multiple cellular activities, such as cancer progression, microbial transduction. Notably, recent studies suggest phase separation regulates RLR cGAS–STING pathways. Moreover, proper proteins replication pathogenesis. These observations indicate checkpoint virus host interaction. In this study, we summarize advances concerning regulation infection by separation. Our review highlights emerging notion robust modulator

Language: Английский

Citations

15
Molecular mechanisms and cellular functions of liquid-liquid phase separation during antiviral immune responses DOI Creative Commons
Shuai Yang,

Weishan Shen,

Jiajia Hu

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: May 10, 2023

Spatiotemporal separation of cellular components is vital to ensure biochemical processes. Membrane-bound organelles such as mitochondria and nuclei play a major role in isolating intracellular components, while membraneless (MLOs) are accumulatively uncovered via liquid-liquid phase (LLPS) mediate spatiotemporal organization. MLOs orchestrate various key processes, including protein localization, supramolecular assembly, gene expression, signal transduction. During viral infection, LLPS not only participates replication but also contributes host antiviral immune responses. Therefore, more comprehensive understanding the roles virus infection may open up new avenues for treating infectious diseases. In this review, we focus on defense mechanisms innate immunity discuss involvement during evasion escape, well strategy targeting treat

Language: Английский

Citations

13