Identification and Characterization of a Novel Protein–Protein Interaction Among SARS-CoV-2 Nucleocapsid, Host SFPQ, and hnRNP U and Its Potential Role in Virus Replication

IF 2.4 4区 生物学 Q4 CELL BIOLOGY
Ashish Agrahari, Km. Archana, Nittu Singh, Akshay Joshi, Budai S. Vivek Vinod, Sourav Haldar, Krishan Gopal Thakur, Raj Kamal Tripathi
{"title":"Identification and Characterization of a Novel Protein–Protein Interaction Among SARS-CoV-2 Nucleocapsid, Host SFPQ, and hnRNP U and Its Potential Role in Virus Replication","authors":"Ashish Agrahari,&nbsp;Km. Archana,&nbsp;Nittu Singh,&nbsp;Akshay Joshi,&nbsp;Budai S. Vivek Vinod,&nbsp;Sourav Haldar,&nbsp;Krishan Gopal Thakur,&nbsp;Raj Kamal Tripathi","doi":"10.1111/boc.70008","DOIUrl":null,"url":null,"abstract":"<div>\n \n <p>SARS-CoV-2 has led to significant global health and economic challenges and caused the COVID-19 pandemic. The ability of the virus to replicate adeptly within host cells is critical for its pathogenicity. The structural nucleocapsid (N) protein of SARS-CoV-2 packages newly synthesized viral RNA with the association of various host proteins that may contribute to different functions in maintaining a productive viral life cycle. In this study, we report the identification and characterization of host proteins SFPQ and hnRNP U interacting with SARS-CoV-2 N protein in both N-transfected cells and virus-infected cells, forming a hetero-trimeric protein complex. Using carefully designed peptides that span the length of N protein and competitive inhibition, we identified the interacting domains at N protein that interact with SFPQ and hnRNP U. Our results constitute the first report that the characterized N protein and host SFPQ and hnRNP U form a hetero-trimeric protein complex in both N transfected cells and virus-infected cells. Utilizing competitive peptides, we were able to disrupt the hetero-trimeric protein complex in virus-infected cells, leading to reduction in viral replication. These results clearly demonstrate that N-SFPQ-hnRNP U hetero-trimeric protein complex formation is found in SARS-CoV-2 infected cells that regulate viral replication. Our findings suggest that the protein–protein interaction (PPI) between N-SFPQ-hnRNP U hetero-trimeric protein complexes could be a novel drug target for developing therapeutics against COVID-19.</p>\n </div>","PeriodicalId":8859,"journal":{"name":"Biology of the Cell","volume":"117 4","pages":""},"PeriodicalIF":2.4000,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biology of the Cell","FirstCategoryId":"99","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/boc.70008","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

SARS-CoV-2 has led to significant global health and economic challenges and caused the COVID-19 pandemic. The ability of the virus to replicate adeptly within host cells is critical for its pathogenicity. The structural nucleocapsid (N) protein of SARS-CoV-2 packages newly synthesized viral RNA with the association of various host proteins that may contribute to different functions in maintaining a productive viral life cycle. In this study, we report the identification and characterization of host proteins SFPQ and hnRNP U interacting with SARS-CoV-2 N protein in both N-transfected cells and virus-infected cells, forming a hetero-trimeric protein complex. Using carefully designed peptides that span the length of N protein and competitive inhibition, we identified the interacting domains at N protein that interact with SFPQ and hnRNP U. Our results constitute the first report that the characterized N protein and host SFPQ and hnRNP U form a hetero-trimeric protein complex in both N transfected cells and virus-infected cells. Utilizing competitive peptides, we were able to disrupt the hetero-trimeric protein complex in virus-infected cells, leading to reduction in viral replication. These results clearly demonstrate that N-SFPQ-hnRNP U hetero-trimeric protein complex formation is found in SARS-CoV-2 infected cells that regulate viral replication. Our findings suggest that the protein–protein interaction (PPI) between N-SFPQ-hnRNP U hetero-trimeric protein complexes could be a novel drug target for developing therapeutics against COVID-19.

Abstract Image

SARS-CoV-2核衣壳、宿主SFPQ和hnRNP U之间一种新的蛋白-蛋白相互作用的鉴定和表征及其在病毒复制中的潜在作用
SARS-CoV-2导致了重大的全球卫生和经济挑战,并导致了COVID-19大流行。病毒在宿主细胞内熟练复制的能力对其致病性至关重要。SARS-CoV-2的结构核衣壳(N)蛋白将新合成的病毒RNA与多种宿主蛋白结合,这些宿主蛋白可能在维持病毒高产生命周期中发挥不同的功能。在这项研究中,我们报道了宿主蛋白SFPQ和hnRNP U在N转染细胞和病毒感染细胞中与sars - cov - 2n蛋白相互作用,形成异源三聚体蛋白复合物的鉴定和表征。利用精心设计的跨N蛋白长度的多肽和竞争性抑制,我们确定了N蛋白上与SFPQ和hnRNP U相互作用的相互作用结构域。我们的研究结果首次报道了特征的N蛋白和宿主SFPQ和hnRNP U在N转染细胞和病毒感染细胞中形成异质三聚体蛋白复合物。利用竞争性肽,我们能够破坏病毒感染细胞中的异三聚体蛋白复合物,导致病毒复制减少。这些结果清楚地表明,在SARS-CoV-2感染的细胞中发现了N-SFPQ-hnRNP - U异三聚体蛋白复合物的形成,并调节病毒复制。我们的研究结果表明,N-SFPQ-hnRNP - U异种三聚体蛋白复合物之间的蛋白-蛋白相互作用(PPI)可能成为开发抗COVID-19治疗药物的新药物靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Biology of the Cell
Biology of the Cell 生物-细胞生物学
CiteScore
5.30
自引率
0.00%
发文量
53
审稿时长
>12 weeks
期刊介绍: The journal publishes original research articles and reviews on all aspects of cellular, molecular and structural biology, developmental biology, cell physiology and evolution. It will publish articles or reviews contributing to the understanding of the elementary biochemical and biophysical principles of live matter organization from the molecular, cellular and tissues scales and organisms. This includes contributions directed towards understanding biochemical and biophysical mechanisms, structure-function relationships with respect to basic cell and tissue functions, development, development/evolution relationship, morphogenesis, stem cell biology, cell biology of disease, plant cell biology, as well as contributions directed toward understanding integrated processes at the organelles, cell and tissue levels. Contributions using approaches such as high resolution imaging, live imaging, quantitative cell biology and integrated biology; as well as those using innovative genetic and epigenetic technologies, ex-vivo tissue engineering, cellular, tissue and integrated functional analysis, and quantitative biology and modeling to demonstrate original biological principles are encouraged.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信