A Single Amino Acid in Human APOBEC3F Alters Susceptibility to HIV-1 Vif
A Single Amino Acid in Human APOBEC3F Alters Susceptibility to HIV-1 Vif
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DOI：
10.1074/jbc.m110.173161
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发表时间：
2010-12-24
影响因子：
4.8
通讯作者：
Harris, Reuben S.
中科院分区：
文献类型：
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作者：
Albin, John S.;LaRue, Rebecca S.;Harris, Reuben S.
人APOBEC 3F（huA 3F）在缺乏病毒辅助蛋白病毒粒子感染因子（Vif）的情况下有效限制HIV-1的感染性。Vif的功能是通过触发huA 3F而不是恒河猴A3 F（rhA 3F）的降解来保持病毒感染性。在这里，我们使用huA 3F和rhA 3F之间的缺失，嵌合体和系统诱变的组合，以确定Glu（324）作为huA 3F对HIV-1 Vif介导的降解敏感性的关键决定因素。huA 3F的C末端脱氨酶结构域的结构模型表明，Glu（324）是α 4螺旋内的表面残基，邻近与APOBEC 3G和APOBEC 3 H中其他已知Vif易感性决定簇对应的残基。这种结构聚类表明Vif可能结合存在于多种APOBEC 3蛋白中的保守表面。
Human APOBEC3F (huA3F) potently restricts the infectivity of HIV-1 in the absence of the viral accessory protein virion infectivity factor (Vif). Vif functions to preserve viral infectivity by triggering the degradation of huA3F but not rhesus macaque A3F (rhA3F). Here, we use a combination of deletions, chimeras, and systematic mutagenesis between huA3F and rhA3F to identify Glu(324) as a critical determinant of huA3F susceptibility to HIV-1 Vif-mediated degradation. A structural model of the C-terminal deaminase domain of huA3F indicates that Glu(324) is a surface residue within the alpha 4 helix adjacent to residues corresponding to other known Vif susceptibility determinants in APOBEC3G and APOBEC3H. This structural clustering suggests that Vif may bind a conserved surface present in multiple APOBEC3 proteins.