Modulation of Biophysical Properties of Nucleocapsid Protein in the Mutant Spectrum of SARS-CoV-2 DOI Open Access

Ai Nguyen,

Huaying Zhao,

Dulguun Myagmarsuren

et al.

Published: May 10, 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 exhibiting 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.

Language: Английский

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

Laura Seddar,

Konstantin von Stromberg

et al.

Journal of Virology, Journal Year: 2024, Volume and Issue: 98(2)

Published: Jan. 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.

Language: Английский

Citations

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

et al.

eLife, Journal Year: 2024, Volume and Issue: 13

Published: Feb. 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.

Language: Английский

Citations

7
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

et al.

International Journal of Biological Sciences, Journal Year: 2024, Volume and Issue: 20(5), P. 1652 - 1668

Published: Jan. 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.

Language: Английский

Citations

6
Modulation of biophysical properties of nucleocapsid protein in the mutant spectrum of SARS-CoV-2 DOI Creative Commons

Ai Nguyen,

Huaying Zhao,

Dulguun Myagmarsuren

et al.

eLife, Journal Year: 2024, Volume and Issue: 13

Published: June 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.

Language: Английский

Citations

6
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
Plant viruses and biomolecular condensates: novel perspectives in virus replication strategies DOI Open Access
Jared P. May

New Phytologist, Journal Year: 2024, Volume and Issue: 243(5), P. 1636 - 1638

Published: April 24, 2024

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

Language: Английский

Citations

5
Interactions between the picornavirus 3C(D) main protease and RNA induce liquid-liquid phase separation DOI Creative Commons
Somnath Mondal, Saumyak Mukherjee, Kevin Namitz

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: April 17, 2025

ABSTRACT The picornavirus 3CD protein is a precursor to the 3C main protease and 3D RNA-dependent RNA polymerase. In addition its functions in proteolytic processing of virus polyprotein cleavage key host factors, domain interacts with cis-acting replication elements (CREs) within viral genome regulate translation events. We investigated molecular determinants binding using wide range biophysical computational methods. These studies showed that binds broad spectrum oligonucleotides, displaying minimal dependence on sequence structure. However, they also uncovered novel aspect these interactions, is, 3C-RNA can induce liquid-liquid phase separation (LLPS), 3CD-RNA interactions likewise leading LLPS. This may be general phenomenon for other 3C-like proteases, incorporating domains. findings have potential implications understanding virally induced apoptosis controlling stress granules, which involve LLPS include proteins known 3C/3CD.

Language: Английский

Citations

0
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
Nucleocytoviricota Viral Factories Are Transient Organelles Made by Phase Separation DOI
Sofia Rigou, Alain Schmitt, Audrey Lartigue

et al.

Published: Sept. 30, 2024

Phase separation is a common mechanism utilized by viruses to achieve replication, host manipulation and virion morphogenesis. The newly defined phylum _Nucleocytoviricota_ encompass ubiquitous diverse including _Poxviridae,_ the climate-modulating _Emiliania huxleyi_ virus previously termed Nucleocytoplasmic large DNA (NCLDV). Cytoplasmic members of this form viral factories but their nature remains unknow. Here we show that these are formed phase separation. We demonstrate mimivirus multilayered using at least two scaffold proteins. also generate pipeline bioinformatically identify putative proteins in all other despite major primary sequence variability. Such predictions were based on conserved molecular grammar governed electrostatic interactions. Scaffold candidates validated for family _Marseilleviridae_ highlighted role H5 as protein poxviruses. Finally, provide repertoire client nucleus-like factory important sub-compartmentalization functions central dogma. Overall, reveal new acquisition nuclear-like entirely re-classified biomolecular condensates.

Language: Английский

Citations

3
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

et al.

Journal of Virological Methods, Journal Year: 2025, Volume and Issue: 335, P. 115147 - 115147

Published: March 6, 2025

Language: Английский

Citations

0