Maturation of the matrix and viral membrane of HIV-1.

Maturation of the matrix and viral membrane of HIV-1.
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DOI:
10.1126/science.abe6821
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发表时间:
2021-08-06
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Briggs JAG
Briggs JAG
中科院分区:
其他
文献类型:
--
作者:
Qu K;Ke Z;Zila V;Anders-Össwein M;Glass B;Mücksch F;Müller R;Schultz C;Müller B;Kräusslich HG;Briggs JAG

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GAG是HIV-1的主要结构蛋白,通过其基质结构域(MA)被募集到质膜上进行病毒组装。GAG随后被切割成其组成部分结构域,导致结构成熟,以改变病毒粒子进入细胞的目的。通过冷冻电子断层扫描,我们确定了未成熟和成熟HIV-1中MA的结构和排列。我们发现MA在成熟后会在两个不同的六面体晶格之间重排。在成熟的HIV-1中,脂质从膜外延伸到MA的口袋中。我们的数据表明,HIV-1的蛋白水解性成熟不仅实现了病毒衣壳在基因组周围的组装,而且延伸到重新利用膜结合的MA晶格来实现进入或进入后的功能,并导致从病毒膜上部分去除多达2500种脂类。
Gag – the main structural protein of HIV-1 – is recruited to the plasma membrane for virus assembly by its matrix (MA) domain. Gag is subsequently cleaved into its component domains, causing structural maturation to repurpose the virion for cell entry. We determined the structure and arrangement of MA within immature and mature HIV-1 by cryo-electron tomography. We found that MA rearranges between two different hexameric lattices upon maturation. In mature HIV-1, a lipid extends out of the membrane to bind a pocket in MA. Our data suggest that proteolytic maturation of HIV-1 not only achieves assembly of the viral capsid surrounding the genome, but extends to repurpose the membrane-bound MA lattice for an entry or post-entry function, and causes partial removal of up to 2,500 lipids from the viral membrane.
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