HIV-1 Nucleocapsid Mimics the Membrane Adaptor Syntenin PDZ to Gain Access to ESCRTs and Promote Virus Budding.
HIV-1 Nucleocapsid Mimics the Membrane Adaptor Syntenin PDZ to Gain Access to ESCRTs and Promote Virus Budding.
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HIV-1 核衣壳模仿膜适配器 Syntenin PDZ 以获得 ESRT 并促进病毒出芽。
DOI：
10.1016/j.chom.2016.02.004
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发表时间：
2016
影响因子：
30.3
通讯作者：
Bouamr,Fadila
中科院分区：
文献类型：
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作者：
Sette,Paola;O'Connor,SarahK;Yerramilli,VSiddartha;Dussupt,Vincent;Nagashima,Kunio;Chutiraka,Kasana;Lingappa,Jaisri;Scarlata,Suzanne;Bouamr,Fadila
HIV-1募集转运所需的细胞内体分选复合物（ESCRT），以从膜上出芽病毒粒子。病毒核衣壳（NC）结构域完整性的破坏影响HIV-1出芽。然而，NC参与HIV出芽的分子机制仍不清楚。我们发现，NC模仿的PDZ结构域的syntenin，膜结合接头参与细胞与细胞的接触/通信，捕获的Bro 1结构域的阿利克斯，这是一个ESCRTs招募细胞适配器。NC通过远端或近端锌指中的碱性残基结合膜，并且NC-膜结合对于Bro 1捕获和HIV-1出芽是必需的。去除RNA增强NC膜结合，表明膜脂质和RNA之间的动态竞争NC中相同的结合位点。值得注意的是，syntenin PDZ可以替代NC在HIV-1出芽中的功能。因此，NC模拟syntenin PDZ作为一个膜结合的适配器的HIV-1在特定的微域的膜出芽的关键功能。
HIV-1 recruits cellular endosomal sorting complexes required for transport (ESCRTs) to bud virions from the membrane. Disruption of the viral nucleocapsid (NC) domain integrity affects HIV-1 budding. However, the molecular mechanisms of NC's involvement in HIV budding remain unclear. We find that NC mimics the PDZ domains of syntenin, a membrane-binding adaptor involved in cell-to-cell contact/communication, to capture the Bro1 domain of ALIX, which is an ESCRTs recruiting cellular adaptor. NC binds membranes via basic residues in either the distal or proximal zinc fingers, and NC-membrane binding is essential for Bro1 capture and HIV-1 budding. Removal of RNA enhances NC membrane binding, suggesting a dynamic competition between membrane lipids and RNA for the same binding sites in NC. Remarkably, syntenin PDZ can substitute for NC function in HIV-1 budding. Thus, NC mimics syntenin PDZs to function as a membrane-binding adaptor critical for HIV-1 budding at specific microdomains of the membrane.