抗病毒HIV-1 SERINC限制因素破坏病毒膜不对称性
Susan A Leonhardt1,2, Michael D Purdy2,3, Jonathan R Grover4
1The Phillip and Patricia Frost Institute for Chemistry and Molecular Science, University of Miami, Coral Gables, FL, 33146, USA.
Nature communications
|July 20, 2023
概括
主体蛋白质SERINC3和SERINC5通过翻转脂质,改变病毒包膜结构来限制HIV-1的感染性. 艾滋病毒-1 Nef 蛋白质抵消了这种效应,突出了 SERINCs 作为病毒进入的关键调节者.
科学领域:
- 病毒学 病毒学
- 结构生物学 结构生物学
- 膜生物学 膜生物学
背景情况:
- SERINC3和SERINC5是抑制HIV-1感染性的宿主限制因素.
- 艾滋病毒-1 Nef 蛋白通过与细胞内循环4 (ICL4) 结合来对抗 SERINC 功能.
研究的目的:
- 为了确定 SERINC3 函数的结构基础.
- 研究SERINCs限制病毒感染性的机制.
- 为了阐明Nef如何对抗SERINC活动.
主要方法:
- 电子显微镜 (cryo-EM) 用于确定人类SERINC3.3的结构.
- 脂质翻转试验使用与纯化的SERINCs复制的蛋白质体.
- 在存在SERINC和病毒蛋白质的情况下分析病毒感染性.
主要成果:
- hSERINC3的冷-EM结构显示出一个独特的结构,由两个α螺旋束连接着一个倾斜的"交叉"螺旋环,类似于非ATP依赖的脂质输送器.
- 纯化hSERINCs诱导酸胺 (PS),酸乙醇胺和酸胆在蛋白质体中的翻转.
- 在SERINC3和SERINC5中,PS暴露在HIV-1和MLV的表面上,降低了它们的感染力,Nef和GlycoGag分别抵消了这种效应.
结论:
- SERINCs作为翻转脂质的膜载体,破坏了膜不对称性.
- 这种膜不对称性损失与病毒包裹 (Env) 形状的变化相关,导致病毒感染能力降低.
- SERINCs代表了针对HIV-1和其他病毒的抗病毒策略的新目标.
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