Structural basis for nuclear import of hepatitis B virus (HBV) nucleocapsid core.

Structural basis for nuclear import of hepatitis B virus (HBV) nucleocapsid core.
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乙型肝炎病毒(HBV)核衣壳核输入的结构基础

DOI:
10.1126/sciadv.adi7606
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发表时间:
2024-01-12
期刊:
影响因子:
13.6
通讯作者:
Cingolani, Gino
Cingolani, Gino
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Yang, Ruoyu;Ko, Ying-Hui;Li, Fenglin;Lokareddy, Ravi K.;Hou, Chun-Feng David;Kim, Christine;Klein, Shelby;Antolinez, Santiago;Marin, Juan F.;Perez-Segura, Carolina;Jarrold, Martin F.;Zlotnick, Adam;Hadden-Perilla, Jodi A.;Cingolani, Gino

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B型肝炎病毒(HBV)核衣壳的核输入对于在核中发生的复制是必不可少的。~360埃的HBV衣壳作为完整颗粒转移到核孔复合体(NPC),在宿主激酶刺激的反应中劫持人类输入蛋白。本文介绍了HBV衣壳识别的重要机制。我们发现importin α1在HBV外壳蛋白Cp 183羧基末端结构域(CTD)的远端结合核定位信号(NLS)。该NLS通过二十面体准六重顶点处的孔暴露于衣壳表面。丝氨酸-155、丝氨酸-162和丝氨酸-170的磷酸化促进CTD压缩,但不影响对importin α1的亲和力。30 importin α1/β1的结合使HBV衣壳直径增加至约620埃,接近可通过NPC的最大尺寸。我们建议,磷酸化有利于CTD外化,并促使其在衣壳表面的压实,暴露的NLS的输入。结合结构和计算方法,研究了人输入蛋白对B型肝炎病毒衣壳蛋白的识别。
Nuclear import of the hepatitis B virus (HBV) nucleocapsid is essential for replication that occurs in the nucleus. The ~360-angstrom HBV capsid translocates to the nuclear pore complex (NPC) as an intact particle, hijacking human importins in a reaction stimulated by host kinases. This paper describes the mechanisms of HBV capsid recognition by importins. We found that importin α1 binds a nuclear localization signal (NLS) at the far end of the HBV coat protein Cp183 carboxyl-terminal domain (CTD). This NLS is exposed to the capsid surface through a pore at the icosahedral quasi-sixfold vertex. Phosphorylation at serine-155, serine-162, and serine-170 promotes CTD compaction but does not affect the affinity for importin α1. The binding of 30 importin α1/β1 augments HBV capsid diameter to ~620 angstroms, close to the maximum size trafficable through the NPC. We propose that phosphorylation favors CTD externalization and prompts its compaction at the capsid surface, exposing the NLS to importins. Hepatitis B virus capsid recognition by human importins was deciphered by combining structural and computational methods.
简单的动力学关系和非特异性竞争控制体内核进口率。
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