Mechanistic Insights Into an Ancient Adenovirus Precursor Protein VII Show Multiple Nuclear Import Receptor Pathways.

IF 3.6 3区 生物学 Q3 CELL BIOLOGY Traffic Pub Date : 2024-09-01 DOI:10.1111/tra.12953
Sepehr Nematollahzadeh, Ajani Athukorala, Camilla M Donnelly, Silvia Pavan, Victoria Atelie-Djossou, Enzo Di Iorio, Babu Nath, Karla J Helbig, Brian P McSharry, Jade K Forwood, Subir Sarker, Gualtiero Alvisi
{"title":"Mechanistic Insights Into an Ancient Adenovirus Precursor Protein VII Show Multiple Nuclear Import Receptor Pathways.","authors":"Sepehr Nematollahzadeh, Ajani Athukorala, Camilla M Donnelly, Silvia Pavan, Victoria Atelie-Djossou, Enzo Di Iorio, Babu Nath, Karla J Helbig, Brian P McSharry, Jade K Forwood, Subir Sarker, Gualtiero Alvisi","doi":"10.1111/tra.12953","DOIUrl":null,"url":null,"abstract":"<p><p>Adenoviral pVII proteins are multifunctional, highly basic, histone-like proteins that can bind to and transport the viral genome into the host cell nucleus. Despite the identification of several nuclear localization signals (NLSs) in the pVII protein of human adenovirus (HAdV)2, the mechanistic details of nuclear transport are largely unknown. Here we provide a full characterization of the nuclear import of precursor (Pre-) pVII protein from an ancient siadenovirus, frog siadenovirus 1 (FrAdV1), using a combination of structural, functional, and biochemical approaches. Two strong NLSs (termed NLSa and NLSd) interact with importin (IMP)β1 and IMPα, respectively, and are the main drivers of nuclear import. A weaker NLS (termed NLSb) also contributes, together with an additional signal (NLSc) which we found to be important for nucleolar targeting and intranuclear binding. Expression of wild-type and NLS defective derivatives Pre-pVII in the presence of selective inhibitors of different nuclear import pathways revealed that, unlike its human counterpart, FrAdV1 Pre-pVII nuclear import is dependent on IMPα/β1 and IMPβ1, but not on transportin-1 (IMPβ2). Clearly, AdVs evolved to maximize the nuclear import pathways for the pVII proteins, whose subcellular localization is the result of a complex process. Therefore, our results pave the way for an evolutionary comparison of the interaction of different AdVs with the host cell nuclear transport machinery.</p>","PeriodicalId":23207,"journal":{"name":"Traffic","volume":null,"pages":null},"PeriodicalIF":3.6000,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Traffic","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1111/tra.12953","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Adenoviral pVII proteins are multifunctional, highly basic, histone-like proteins that can bind to and transport the viral genome into the host cell nucleus. Despite the identification of several nuclear localization signals (NLSs) in the pVII protein of human adenovirus (HAdV)2, the mechanistic details of nuclear transport are largely unknown. Here we provide a full characterization of the nuclear import of precursor (Pre-) pVII protein from an ancient siadenovirus, frog siadenovirus 1 (FrAdV1), using a combination of structural, functional, and biochemical approaches. Two strong NLSs (termed NLSa and NLSd) interact with importin (IMP)β1 and IMPα, respectively, and are the main drivers of nuclear import. A weaker NLS (termed NLSb) also contributes, together with an additional signal (NLSc) which we found to be important for nucleolar targeting and intranuclear binding. Expression of wild-type and NLS defective derivatives Pre-pVII in the presence of selective inhibitors of different nuclear import pathways revealed that, unlike its human counterpart, FrAdV1 Pre-pVII nuclear import is dependent on IMPα/β1 and IMPβ1, but not on transportin-1 (IMPβ2). Clearly, AdVs evolved to maximize the nuclear import pathways for the pVII proteins, whose subcellular localization is the result of a complex process. Therefore, our results pave the way for an evolutionary comparison of the interaction of different AdVs with the host cell nuclear transport machinery.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
对一种古老腺病毒前体蛋白 VII 的机理研究显示了多种核导入受体途径。
腺病毒 pVII 蛋白是一种多功能、高碱性的组蛋白样蛋白,可与病毒基因组结合并将其转运到宿主细胞核中。尽管在人腺病毒(HAdV)2 的 pVII 蛋白中发现了几个核定位信号(NLS),但核转运的机制细节在很大程度上仍不为人所知。在这里,我们结合结构、功能和生化方法,对古老的 siadenovirus--青蛙 siadenovirus 1(FrAdV1)的前体(Pre-)pVII 蛋白的核输入进行了全面鉴定。两个强NLS(称为NLSa和NLSd)分别与导入素(IMP)β1和IMPα相互作用,是核导入的主要驱动力。一个较弱的 NLS(称为 NLSb)也有作用,另外还有一个信号(NLSc),我们发现该信号对核靶向和核内结合非常重要。在不同核导入途径的选择性抑制剂作用下,野生型和 NLS 缺陷衍生物 Pre-pVII 的表达显示,与人类不同,FrAdV1 Pre-pVII 的核导入依赖于 IMPα/β1 和 IMPβ1,但不依赖于转运蛋白-1(IMPβ2)。显然,AdVs 的进化是为了最大化 pVII 蛋白的核导入途径,而其亚细胞定位是一个复杂过程的结果。因此,我们的研究结果为比较不同 AdV 与宿主细胞核转运机制相互作用的进化过程铺平了道路。
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 去求助
来源期刊
Traffic
Traffic 生物-细胞生物学
CiteScore
8.10
自引率
2.20%
发文量
50
审稿时长
2 months
期刊介绍: Traffic encourages and facilitates the publication of papers in any field relating to intracellular transport in health and disease. Traffic papers span disciplines such as developmental biology, neuroscience, innate and adaptive immunity, epithelial cell biology, intracellular pathogens and host-pathogen interactions, among others using any eukaryotic model system. Areas of particular interest include protein, nucleic acid and lipid traffic, molecular motors, intracellular pathogens, intracellular proteolysis, nuclear import and export, cytokinesis and the cell cycle, the interface between signaling and trafficking or localization, protein translocation, the cell biology of adaptive an innate immunity, organelle biogenesis, metabolism, cell polarity and organization, and organelle movement. All aspects of the structural, molecular biology, biochemistry, genetics, morphology, intracellular signaling and relationship to hereditary or infectious diseases will be covered. Manuscripts must provide a clear conceptual or mechanistic advance. The editors will reject papers that require major changes, including addition of significant experimental data or other significant revision. Traffic will consider manuscripts of any length, but encourages authors to limit their papers to 16 typeset pages or less.
期刊最新文献
Fluorescent Reporters, Imaging, and Artificial Intelligence Toolkits to Monitor and Quantify Autophagy, Heterophagy, and Lysosomal Trafficking Fluxes. Intercellular Mitochondrial Transfer: The Novel Therapeutic Mechanism for Diseases. Mechanistic Insights Into an Ancient Adenovirus Precursor Protein VII Show Multiple Nuclear Import Receptor Pathways. Dissociation of Drosophila Evi-Wg Complex Occurs Post Apical Internalization in the Maturing Acidic Endosomes. Post-Transcriptional Regulation of Rab7a in Lysosomal Positioning and Drug Resistance in Nutrient-Limited Cancer Cells.
×
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
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 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 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1