Experimental Considerations for the Evaluation of Viral Biomolecular Condensates DOI
Christine Roden, Amy S. Gladfelter

Annual Review of Virology, Год журнала: 2024, Номер 11(1), С. 105 - 124

Опубликована: Сен. 26, 2024

Biomolecular condensates are nonmembrane-bound assemblies of biological polymers such as protein and nucleic acids. An increasingly accepted paradigm across the viral tree life is (a) that viruses form biomolecular (b) formation required for virus. Condensates can promote replication by promoting packaging, genome compaction, membrane bending, co-opting host translation. This review primarily concerned with exploring methodologies assessing virally encoded condensates. The goal this to provide an experimental framework virologists consider when designing experiments identify their components, reconstitute condensation cell free from minimal (c) ask questions about what conditions lead condensation, (d) map these back cycle, (e) design test inhibitors/modulators potential therapeutics. attempts integrate virology, biology, biochemistry approaches.

Язык: Английский

The adenovirus DNA-binding protein DBP DOI
Luca D. Bertzbach,

Laura Seddar,

Konstantin von Stromberg

и другие.

Journal of Virology, Год журнала: 2024, Номер 98(2)

Опубликована: Янв. 10, 2024

Adenoviruses are a group of double-stranded DNA viruses that can mainly cause respiratory, gastrointestinal, and eye infections in humans. In addition, adenoviruses employed as vector vaccines for combatting viral infections, including SARS-CoV-2, serve excellent gene therapy vectors. These have the ability to modulate host cell machinery their advantage trigger significant restructuring nuclei infected cells through activity proteins. One those, adenovirus DNA-binding protein (DBP), is multifunctional non-structural integral reorganization processes. DBP encoded E2A transcriptional unit highly abundant cells. Its unequivocally linked formation, structure, integrity virus-induced replication compartments, molecular hubs regulation processes, control cell. also plays key roles replication, transcription, expression, even range specificity. Notably, post-translational modifications DBP, such SUMOylation extensive phosphorylation, regulate its biological functions. was first investigated 1970s, pioneering research on this literature review, we provide an overview specifically summarize findings related complex diverse functions, role context replication. Finally, address novel insights perspectives future research.

Язык: Английский

Процитировано

9

Modulation of biophysical properties of nucleocapsid protein in the mutant spectrum of SARS-CoV-2 DOI Creative Commons

Ai Nguyen,

Huaying Zhao,

Dulguun Myagmarsuren

и другие.

eLife, Год журнала: 2024, Номер 13

Опубликована: Фев. 6, 2024

Genetic diversity is a hallmark of RNA viruses and the basis for their evolutionary success. Taking advantage uniquely large genomic database SARS-CoV-2, we examine impact mutations across spectrum viable amino acid sequences on biophysical phenotypes highly expressed multifunctional nucleocapsid protein. We find variation in physicochemical parameters its extended intrinsically disordered regions (IDRs) sufficient to allow local plasticity, but also observe functional constraints that similarly occur related coronaviruses. In experiments with several N-protein species carrying associated major variants, point IDRs can have nonlocal modulate thermodynamic stability, secondary structure, protein oligomeric state, particle formation, liquid-liquid phase separation. Omicron variant, distant different compensatory effects shifting delicate balance interactions controlling assembly properties, include creation new protein-protein interaction interface N-terminal IDR through defining P13L mutation. A picture emerges where genetic accompanied by significant characteristics species, particular IDRs.

Язык: Английский

Процитировано

9

The Burgeoning Significance of Liquid-Liquid Phase Separation in the Pathogenesis and Therapeutics of Cancers DOI Creative Commons

Wei-Xin Xu,

Qiang Qu,

Hai-Hui Zhuang

и другие.

International Journal of Biological Sciences, Год журнала: 2024, Номер 20(5), С. 1652 - 1668

Опубликована: Янв. 1, 2024

Liquid-liquid phase separation (LLPS) is a physiological phenomenon that parallels the mixing of oil and water, giving rise to compartments with diverse physical properties.Biomolecular condensates, arising from LLPS, serve as critical regulators gene expression control, particular significance in context malignant tumors.Recent investigations have unveiled intimate connection between LLPS cancer, nexus profoundly impacts various facets cancer progression, including DNA repair, transcriptional regulation, oncogene expression, formation membraneless organelles within microenvironment.This review provides comprehensive account evolution molecular pathological level.We explore mechanisms by through which biomolecular condensates govern cellular processes, encompassing signal transduction, responses environmental stressors.Furthermore, we concentrate on potential therapeutic targets development small-molecule inhibitors associated prevalent clinical malignancies.Understanding role its interplay tumor milieu holds promise for enhancing treatment strategies, particularly overcoming drug resistance challenges.These insights offer innovative perspectives support advancing therapy.

Язык: Английский

Процитировано

7

Modulation of biophysical properties of nucleocapsid protein in the mutant spectrum of SARS-CoV-2 DOI Creative Commons

Ai Nguyen,

Huaying Zhao,

Dulguun Myagmarsuren

и другие.

eLife, Год журнала: 2024, Номер 13

Опубликована: Июнь 28, 2024

Genetic diversity is a hallmark of RNA viruses and the basis for their evolutionary success. Taking advantage uniquely large genomic database SARS-CoV-2, we examine impact mutations across spectrum viable amino acid sequences on biophysical phenotypes highly expressed multifunctional nucleocapsid protein. We find variation in physicochemical parameters its extended intrinsically disordered regions (IDRs) sufficient to allow local plasticity, but also observe functional constraints that similarly occur related coronaviruses. In experiments with several N-protein species carrying associated major variants, point IDRs can have nonlocal modulate thermodynamic stability, secondary structure, protein oligomeric state, particle formation, liquid-liquid phase separation. Omicron variant, distant different compensatory effects shifting delicate balance interactions controlling assembly properties, include creation new protein-protein interaction interface N-terminal IDR through defining P13L mutation. A picture emerges where genetic accompanied by significant characteristics species, particular IDRs.

Язык: Английский

Процитировано

7

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

Weishan Shen,

Jiajia Hu

и другие.

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Май 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

Язык: Английский

Процитировано

13

Plant viruses and biomolecular condensates: novel perspectives in virus replication strategies DOI Open Access
Jared P. May

New Phytologist, Год журнала: 2024, Номер 243(5), С. 1636 - 1638

Опубликована: Апрель 24, 2024

This article is a Commentary on Lin & Nagy (2024), 243 : 1917–1935.

Язык: Английский

Процитировано

5

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

и другие.

Journal of Cellular Biochemistry, Год журнала: 2024, Номер 125(7)

Опубликована: Июнь 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.

Язык: Английский

Процитировано

4

Liquid-liquid phase separation: a new perspective on respiratory diseases DOI Creative Commons
Li Wang, Yongjun Wang, Z. J. Ke

и другие.

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Сен. 26, 2024

Liquid-liquid phase separation (LLPS) is integral to various biological processes, facilitating signal transduction by creating a condensed, membrane-less environment that plays crucial roles in diverse physiological and pathological processes. Recent evidence has underscored the significance of LLPS human health disease. However, its implications respiratory diseases remain poorly understood. This review explores current insights into mechanisms LLPS, focusing particularly on relevance diseases, aiming deepen our understanding propose new paradigm for studying this context.

Язык: Английский

Процитировано

4

Cellular nucleic acid-binding protein restricts SARS-CoV-2 by regulating interferon and disrupting RNA–protein condensates DOI Creative Commons
Yongzhi Chen, Xuqiu Lei, Zhaozhao Jiang

и другие.

Proceedings of the National Academy of Sciences, Год журнала: 2023, Номер 120(47)

Опубликована: Ноя. 14, 2023

A detailed understanding of the innate immune mechanisms involved in restricting SARS-CoV-2 infection and how virus disrupts these processes could reveal new strategies to boost antiviral develop therapeutics for COVID-19. Here, we identify cellular nucleic acid-binding protein (CNBP) as a key host factor controlling infection. In response RNA-sensing pathways, CNBP is phosphorylated translocates from cytosol nucleus where it binds interferon-β enhancer initiate transcription. Because evades detection by host’s largely retained restricts directly, leading battle between that extends beyond signaling pathways. We further demonstrated viral RNA directly competes with nucleocapsid prevent forming liquid–liquid phase separation (LLPS) condensates critical replication. Consequently, cells animals lacking have higher loads, CNBP-deficient mice succumb rapidly Altogether, findings SARS-CoV-2, functioning both regulator IFN gene expression cell-intrinsic restriction LLPS limit replication spread. addition, our studies also highlight important targets development drugs combat

Язык: Английский

Процитировано

9

Attenuation of viral replication foci in nuclei by 1,6 Hexanediol implicates phase separation in the assembly of baculoviral replication factories DOI
Alexander D. Finoshin, О. И. Кравчук, K. I. Adameyko

и другие.

Journal of Virological Methods, Год журнала: 2025, Номер 335, С. 115147 - 115147

Опубликована: Март 6, 2025

Язык: Английский

Процитировано

0