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A bipartite structural organization defines the SERINC family of HIV-1 restriction factors
Nature Structural & Molecular Biology ( IF 12.5 ) Pub Date : 2020-01-06 , DOI: 10.1038/s41594-019-0357-0
Valerie E Pye 1 , Annachiara Rosa 1 , Cinzia Bertelli 2 , Weston B Struwe 3 , Sarah L Maslen 4 , Robin Corey 5 , Idlir Liko 3 , Mark Hassall 6 , Giada Mattiuzzo 6 , Allison Ballandras-Colas 1 , Andrea Nans 7 , Yasuhiro Takeuchi 6, 8 , Phillip J Stansfeld 5, 9 , J Mark Skehel 4 , Carol V Robinson 3 , Massimo Pizzato 2 , Peter Cherepanov 1, 10
Affiliation  

The human integral membrane protein SERINC5 potently restricts HIV-1 infectivity and sensitizes the virus to antibody-mediated neutralization. Here, using cryo-EM, we determine the structures of human SERINC5 and its orthologue from Drosophila melanogaster at subnanometer and near-atomic resolution, respectively. The structures reveal a novel fold comprised of ten transmembrane helices organized into two subdomains and bisected by a long diagonal helix. A lipid binding groove and clusters of conserved residues highlight potential functional sites. A structure-based mutagenesis scan identified surface-exposed regions and the interface between the subdomains of SERINC5 as critical for HIV-1-restriction activity. The same regions are also important for viral sensitization to neutralizing antibodies, directly linking the antiviral activity of SERINC5 with remodeling of the HIV-1 envelope glycoprotein.



中文翻译:


双向结构组织定义了 HIV-1 限制因子的 SERINC 家族



人类整合膜蛋白 SERINC5 有效限制 HIV-1 的感染性并使病毒对抗体介导的中和作用敏感。在这里,我们使用冷冻电镜,分别以亚纳米和近原子分辨率确定了人类 SERINC5 及其来自果蝇的直系同源物的结构。这些结构揭示了一种新颖的折叠,由十个跨膜螺旋组成,这些螺旋组织成两个子域,并被长对角螺旋一分为二。脂质结合沟和保守残基簇突出了潜在的功能位点。基于结构的诱变扫描发现表面暴露区域和 SERINC5 子结构域之间的界面对于 HIV-1 限制活性至关重要。这些区域对于病毒对中和抗体的敏感性也很重要,将 SERINC5 的抗病毒活性与 HIV-1 包膜糖蛋白的重塑直接联系起来。

更新日期:2020-01-06
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