HIV-1 Nef hijacks clathrin coats by stabilizing AP-1:Arf1 polygons.
HIV-1 Nef hijacks clathrin coats by stabilizing AP-1:Arf1 polygons.
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DOI：
10.1126/science.aac5137
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发表时间：
2015-10-23
期刊：
影响因子：
--
通讯作者：
Hurley JH
中科院分区：
文献类型：
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作者：
Shen QT;Ren X;Zhang R;Lee IH;Hurley JH
慢病毒HIV和SIV作为其复制周期的一部分，颠覆了细胞膜的运输。慢病毒Nef蛋白通过劫持AP-1和-2网状蛋白适配器来帮助病毒逃避先天和适应性免疫防御。在这里，我们发现HIV-1Nef和GTPase Arf1诱导AP-1的三聚化和激活。我们报道了Nef和Arf1结合的AP-1三聚体在激活和非激活状态下的冷冻电子显微镜结构。三个Arf1分子的中心核组织了三个三聚体。我们将开放的三聚体与已知的二聚体结构结合在一起，预测了一个六角形的组装，其内外表面分别结合了膜和笼状蛋白。该模型直接可视化，并通过重构笼型组件对模型进行了验证。Arf1和Nef因此在变构激活、货物募集和涂层组装中扮演着相互关联的角色，揭示了网状蛋白涂层内部AP-1层出人意料的复杂组织。
The lentiviruses HIV and SIV subvert intracellular membrane traffic as part of their replication cycle. The lentiviral Nef protein helps viruses evade innate and adaptive immune defenses by hijacking the AP-1 and -2 clathrin adaptors. Here we found that HIV-1 Nef and the GTPase Arf1 induced trimerization and activation of AP-1. We report the cryoelectron microscopy structures of the Nef and Arf1-bound AP-1 trimer in active and inactive states. A central nucleus of three Arf1 molecules organizes the trimers. We combined the open trimer with a known dimer structure, which predicted a hexagonal assembly whose inner and outer faces bind the membranes and clathrin, respectively. Hexagons were directly visualized and the model validated by reconstituting clathrin cage assembly. Arf1 and Nef thus play interconnected roles in allosteric activation, cargo recruitment, and coat assembly, revealing an unexpectedly intricate organization of the inner AP-1 layer of the clathrin coat.