Seeing Biomolecular Condensates Through the Lens of Viruses DOI Creative Commons
Alexander Borodavka, Julia Acker

Annual Review of Virology, Год журнала: 2023, Номер 10(1), С. 163 - 182

Опубликована: Апрель 11, 2023

Phase separation of viral biopolymers is a key factor in the formation cytoplasmic inclusions, known as sites virus replication and assembly. This review describes mechanisms factors that affect phase identifies potential areas for future research. Drawing inspiration from studies on cellular RNA-rich condensates, we compare hierarchical coassembly ribosomal RNAs proteins nucleolus to coordinated taking place within factories viruses containing segmented RNA genomes. We highlight common characteristics biomolecular condensates how this new understanding reshaping our views assembly mechanisms. Such have uncover unexplored antiviral strategies targeting these phase-separated states.

Язык: Английский

Self-assembly coupled to liquid-liquid phase separation DOI Creative Commons
Michael F. Hagan, Farzaneh Mohajerani

PLoS Computational Biology, Год журнала: 2023, Номер 19(5), С. e1010652 - e1010652

Опубликована: Май 15, 2023

Liquid condensate droplets with distinct compositions of proteins and nucleic acids are widespread in biological cells. While it is known that such droplets, or compartments, can regulate irreversible protein aggregation, their effect on reversible self-assembly remains largely unexplored. In this article, we use kinetic theory solution thermodynamics to investigate the liquid-liquid phase separation structures well-defined sizes architectures. We find that, when assembling subunits preferentially partition into liquid robustness against traps maximum achievable assembly rates be significantly increased. particular, both range conditions leading productive corresponding increase by orders magnitude. analyze rate equation predictions using simple scaling estimates identify effects as a function relevant control parameters. These results may elucidate processes underlie normal cellular functions pathogenesis, suggest strategies for designing efficient bottom-up nanomaterials applications.

Язык: Английский

Процитировано

17

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

и другие.

Journal of Cellular Biochemistry, Год журнала: 2024, Номер 125(3)

Опубликована: Фев. 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.

Язык: Английский

Процитировано

9

Scaffolding viral protein NC nucleates phase separation of the HIV-1 biomolecular condensate DOI Creative Commons
Anne Monette,

Meijuan Niu,

Maya Nijhoff Asser

и другие.

Cell Reports, Год журнала: 2022, Номер 40(8), С. 111251 - 111251

Опубликована: Авг. 1, 2022

Membraneless biomolecular condensates (BMCs) contribute to the replication of a growing number viruses but remain be functionally characterized. Previously, we demonstrated that pan-retroviral nucleocapsid (NC) proteins phase separated into regulating virus assembly. Here discover intrinsically disordered human immunodeficiency virus-type 1 (HIV-1) core condense with viral genomic RNA (vRNA) assemble as BMCs attaining geometry characteristic reverse transcription complexes. We explore predisposition, mechanisms, and pharmacologic sensitivity HIV-1 in living cells. vRNA-interacting NC were found scaffolds onto which client capsid, transcriptase, integrase assemble. exhibit fundamental characteristics are drug-sensitive. Lastly, protease-mediated maturation Gag Gag-Pol precursor yield abundant visible This study redefines components fluid advances our understanding nature cores during ingress.

Язык: Английский

Процитировано

28

Protein conformation and biomolecular condensates DOI Creative Commons
Diego S. Vazquez,

Pamela L. Toledo,

Alejo R. Gianotti

и другие.

Current Research in Structural Biology, Год журнала: 2022, Номер 4, С. 285 - 307

Опубликована: Янв. 1, 2022

Protein conformation and cell compartmentalization are fundamental concepts subjects of vast scientific endeavors. In the last two decades, we have witnessed exciting advances that unveiled conjunction these concepts. An avalanche studies highlighted central role biomolecular condensates in membraneless subcellular permits spatiotemporal organization regulation myriads simultaneous biochemical reactions macromolecular interactions. These also shown condensation, driven by multivalent intermolecular interactions, is mediated order-disorder transitions protein domain architecture. Conceptually, condensation a distinct level conformational landscape which collective folding large collections molecules takes place. Biomolecular arise physical process phase separation comprise variety bodies ranging from organelles to liquid solid-like conglomerates, spanning lengths mesoscopic clusters (nanometers) micrometer-sized objects. this review, summarize discuss recent work on assembly, composition, conformation, material properties, thermodynamics, regulation, functions bodies. We review conceptual framework for future dynamics condensed proteins cellular processes.

Язык: Английский

Процитировано

25

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

и другие.

Journal of Virology, Год журнала: 2023, Номер 97(2)

Опубликована: Фев. 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.

Язык: Английский

Процитировано

14

Extending fluorescence anisotropy to large complexes using reversibly switchable proteins DOI Creative Commons
Andrea Volpato, Dirk Ollech, Jonatan Alvelid

и другие.

Nature Biotechnology, Год журнала: 2022, Номер 41(4), С. 552 - 559

Опубликована: Окт. 10, 2022

Abstract The formation of macromolecular complexes can be measured by detection changes in rotational mobility using time-resolved fluorescence anisotropy. However, this method is limited to relatively small molecules (~0.1–30 kDa), excluding the majority human proteome and its complexes. We describe selective anisotropy with reversibly switchable states (STARSS), which overcomes limitation extends observable mass range more than three orders magnitude. STARSS based on long-lived reversible molecular transitions fluorescent proteins resolve slow diffusivity large used probe several cells, including chromatin, retroviral Gag lattice activity-regulated cytoskeleton-associated protein oligomers. Because arbitrarily structures, it generally applicable entire proteome.

Язык: Английский

Процитировано

18

Membraneless Organelles and Condensates Orchestrate Innate Immunity Against Viruses DOI Open Access
Graciela L. Boccaccio, María Gabriela Thomas, Cybele C. Garcı́a

и другие.

Journal of Molecular Biology, Год журнала: 2023, Номер 435(16), С. 167976 - 167976

Опубликована: Янв. 23, 2023

Язык: Английский

Процитировано

10

Biomolecular Condensates as Novel Antiviral Targets DOI Open Access
Erik Martin, Christiane Iserman, Balaji Olety

и другие.

Journal of Molecular Biology, Год журнала: 2023, Номер 436(4), С. 168380 - 168380

Опубликована: Дек. 5, 2023

Язык: Английский

Процитировано

10

Subversion of selective autophagy for the biogenesis of tombusvirus replication organelles inhibits autophagy DOI Creative Commons
Yuanrong Kang, Wenwu Lin, Peter D. Nagy

и другие.

PLoS Pathogens, Год журнала: 2024, Номер 20(3), С. e1012085 - e1012085

Опубликована: Март 14, 2024

Elaborate viral replication organelles (VROs) are formed to support positive-strand RNA virus in infected cells. VRO formation requires subversion of intracellular membranes by proteins. Here, we showed that the key ATG8f autophagy protein and NBR1 selective receptor were co-opted Tomato bushy stunt (TBSV) closely-related carnation Italian ringspot virus. Knockdown or plants led reduced tombusvirus replication, suggesting pro-viral function for autophagy. BiFC proximity-labeling experiments TBSV p33 interacted with recruit them VROs. In addition, observed several core proteins, such as ATG1a, ATG4, ATG5, ATG101 plant-specific SH3P2 adaptor proteins also re-localized VROs, hijacks machinery plant We demonstrated components facilitated recruitment VPS34 PI3 kinase enrichment phospholipids, phosphatidylethanolamine PI3P phosphoinositide membranes. Hijacking into VROs inhibition autophagic flux. found a fraction subverted was sequestered biomolecular condensates associated propose VRO-associated trap those taking away from pathway. Overall, tombusviruses hijack provide phospholipid-rich regulate antiviral

Язык: Английский

Процитировано

4

Exploring the expanding universe of host-virus interactions mediated by viral RNA DOI Creative Commons
Alfredo Castelló, Lucı́a Álvarez, Wael Kamel

и другие.

Molecular Cell, Год журнала: 2024, Номер 84(19), С. 3706 - 3721

Опубликована: Окт. 1, 2024

Язык: Английский

Процитировано

4