HIV-1 matrix-tRNA complex structure reveals basis for host control of Gag localization.
HIV-1 matrix-tRNA complex structure reveals basis for host control of Gag localization.
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DOI：
10.1016/j.chom.2021.07.006
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发表时间：
2021-09-08
影响因子：
30.3
通讯作者：
Zhang J
中科院分区：
文献类型：
--
作者：
Bou-Nader C;Muecksch F;Brown JB;Gordon JM;York A;Peng C;Ghirlando R;Summers MF;Bieniasz PD;Zhang J
HIV-1病毒粒子结构多蛋白Gag通过其n端基质（MA）结构域被定向到质膜上的颗粒组装位点。MA也与宿主trna结合。为了了解MA-tRNA相互作用的分子基础及其潜在功能，我们提出了HIV-1 MA-tRNALys3复合物的共晶结构。该结构揭示了一组特殊的MA碱性和芳香残基，预先配置以识别tRNA肘部的独特结构。突变、交联、荧光和核磁共振分析表明，晶体学定义的界面驱动MA-tRNA在溶液和活细胞中的结合。这种结构表明MA不可能同时结合tRNA和膜。因此，取消MA-tRNA结合的单氨基酸取代导致Gag在质膜上的重新分布，并减少了HIV-1的复制。因此，HIV-1利用宿主trna来阻断膜定位信号并控制其主要结构蛋白的亚细胞分布。宿主trna与HIV-1 Gag基质结构域相互作用，将Gag靶向至质膜。bour - nader等人解决了HIV-1基质与人类tRNALys3结合的共晶结构，并揭示了tRNA“肘部”的特异性识别允许HIV-1利用宿主tRNA来调节Gag定位和病毒粒子组装。
The HIV-1 virion structural polyprotein, Gag, is directed to particle assembly sites at the plasma membrane by its N-terminal Matrix (MA) domain. MA also binds to host tRNAs. To understand the molecular basis of MA-tRNA interaction and its potential function, we present a co-crystal structure of HIV-1 MA-tRNALys3 complex. The structure reveals a specialized group of MA basic and aromatic residues preconfigured to recognize the distinctive structure of the tRNA elbow. Mutational, crosslinking, fluorescence and NMR analyses show that the crystallographically defined interface drives MA-tRNA binding in solution and living cells. The structure indicates that MA is unlikely to bind tRNA and membrane simultaneously. Accordingly, single amino-acid substitutions that abolish MA-tRNA binding caused striking redistribution of Gag to the plasma membrane and reduced HIV-1 replication. Thus, HIV-1 exploits host tRNAs to occlude a membrane localization signal and control the subcellular distribution of its major structural protein. Host tRNAs interact with HIV-1 Gag matrix domain which targets Gag to the plasma membrane. Bou-Nader et al., solve a co-crystal structure of HIV-1 matrix bound to human tRNALys3, and reveal that specific recognition of tRNA “elbow” allows HIV-1 to exploit host tRNAs to regulate Gag localization and virion assembly.
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影响因子：
14.9
作者：
Bou-Nader, Charles;Barraud, Pierre;Hamdane, Djemel
通讯作者：
Hamdane, Djemel
影响因子：
5.4
作者：
Cimarelli, A;Luban, J
通讯作者：
Luban, J
DOI：
10.1073/pnas.86.15.5781
发表时间：
1989-08-01
影响因子：
11.1
作者：
GOTTLINGER, HG;SODROSKI, JG;HASELTINE, WA
通讯作者：
HASELTINE, WA
DOI：
10.1146/annurev-virology-092917-043448
发表时间：
2018-01-01
期刊：
ANNUAL REVIEW OF VIROLOGY, VOL 5
影响因子：
--
作者：
Bieniasz, Paul;Telesnitsky, Alice
通讯作者：
Telesnitsky, Alice
影响因子：
5.6
作者：
Gaines, Christy R.;Tkacik, Emre;Summers, Michael F.
通讯作者：
Summers, Michael F.