Structural insights into HIV-2 CA lattice formation and FG-pocket binding revealed by single-particle cryo-EM.

IF 6.9 1区生物学 Q1 CELL BIOLOGY Cell reports Pub Date : 2025-02-25 Epub Date: 2025-01-25 DOI:10.1016/j.celrep.2025.115245

Matthew Cook, Christian Freniere, Chunxiang Wu, Faith Lozano, Yong Xiong

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Abstract

One of the striking features of human immunodeficiency virus (HIV) is the capsid, a fullerene cone comprised of pleomorphic capsid protein (CA) that shields the viral genome and recruits cofactors. Despite significant advances in understanding the mechanisms of HIV-1 CA assembly and host factor interactions, HIV-2 CA assembly remains poorly understood. By templating the assembly of HIV-2 CA on functionalized liposomes, we report high-resolution structures of the HIV-2 CA lattice, including both CA hexamers and pentamers, alone and with peptides of host phenylalanine-glycine (FG)-motif proteins Nup153 and CPSF6. While the overall fold and mode of FG-peptide binding is conserved with HIV-1, this study reveals distinctive features of the HIV-2 CA lattice, including differing structural character at regions of host factor interactions and divergence in the mechanism of formation of CA hexamers and pentamers. This study extends our understanding of HIV capsids and highlights an approach facilitating the study of lentiviral capsid biology.

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单粒子冷冻电镜揭示了HIV-2 CA晶格形成和fg -口袋结合的结构见解。

人类免疫缺陷病毒（HIV）的一个显著特征是衣壳，一个由多形性衣壳蛋白（CA）组成的富勒烯锥体，可以保护病毒基因组并招募辅助因子。尽管在了解HIV-1 CA组装和宿主因子相互作用的机制方面取得了重大进展，但对HIV-2 CA组装的了解仍然很少。通过在功能化脂质体上模板组装HIV-2 CA，我们报道了HIV-2 CA晶格的高分辨率结构，包括CA六聚体和五聚体，单独和与宿主苯丙氨酸-甘氨酸(FG)-基板蛋白Nup153和CPSF6的肽。虽然fg肽结合的整体折叠和模式在HIV-1中是保守的，但本研究揭示了HIV-2 CA晶格的独特特征，包括宿主因子相互作用区域的不同结构特征以及CA六聚体和五聚体形成机制的差异。这项研究扩展了我们对HIV衣壳的理解，并强调了一种促进慢病毒衣壳生物学研究的方法。

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来源期刊

Cell reports CELL BIOLOGY-

CiteScore

13.80

自引率

1.10%

发文量

1305

审稿时长

77 days

期刊介绍： Cell Reports publishes high-quality research across the life sciences and focuses on new biological insight as its primary criterion for publication. The journal offers three primary article types: Reports, which are shorter single-point articles, research articles, which are longer and provide deeper mechanistic insights, and resources, which highlight significant technical advances or major informational datasets that contribute to biological advances. Reviews covering recent literature in emerging and active fields are also accepted. The Cell Reports Portfolio includes gold open-access journals that cover life, medical, and physical sciences, and its mission is to make cutting-edge research and methodologies available to a wide readership. The journal's professional in-house editors work closely with authors, reviewers, and the scientific advisory board, which consists of current and future leaders in their respective fields. The advisory board guides the scope, content, and quality of the journal, but editorial decisions are independently made by the in-house scientific editors of Cell Reports.