Identification of human MVB12 proteins as ESCRT-I Subunits that function in HIV budding
Identification of human MVB12 proteins as ESCRT-I Subunits that function in HIV budding
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DOI：
10.1016/j.chom.2007.06.003
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发表时间：
2007-07-01
影响因子：
30.3
通讯作者：
Sundquist, Wesley I.
中科院分区：
文献类型：
--
作者：
Morita, Eiji;Sandrin, Virginie;Sundquist, Wesley I.
人ESCRT-1是一种多蛋白复合物，在HIV出芽和内体蛋白分选中发挥重要作用。所有ESCRT-1复合物都含有三个共同的亚基（TSG 101，VPS 28和VPS 37），最近鉴定出酵母ESCRT-1的第四个亚基（Mvb 12 p）。我们现在证明，两个相关的人类蛋白质（MVB 12 A和MVB 12 B）构成的第四类后生动物ESCRT-1亚基，尽管缺乏可识别的序列同源性Mvb 12 p。流体动力学研究表明，可溶性人ESCRT-1复合物含有四种亚基类型中的每一种的一个拷贝。MVB 12亚基通过保守的C-末端序列元件与二元TSG 101-VPS 37复合物的核心区域相关联。MVB 12缺失和过表达均抑制HIV-1感染性并诱导不寻常的病毒组装缺陷，包括异常病毒体形态和改变的病毒Gag蛋白加工。总之，这些研究确定了人ESCRT-1复合物的组成，并表明MVB 12亚基在调节ESCRT介导的病毒出芽中起着独特的作用。
Human ESCRT-1 is a multiprotein complex that plays essential roles in HIV budding and endosomal protein sorting. All ESCRT-1 complexes contain three common subunits (TSG101, VPS28, and VPS37), and a fourth subunit of yeast ESCRT-1 was recently identified (Mvb12p). We now demonstrate that two related human proteins (MVB12A and MVB12B) constitute the fourth class of metazoan ESCRT-1 subunits, despite lacking identifiable sequence homology to Mvb12p. Hydrodynamic studies indicate that soluble human ESCRT-1 complexes contain one copy of each of the four subunit types. MVB12 subunits associate with the core region of the binary TSG101-VPS37 complex through conserved C-terminal sequence elements. Both MVB12 depletion and overexpression inhibit HIV-1 infectivity and induce unusual viral assembly defects, including aberrant virion morphologies and altered viral Gag protein processing. Taken together, these studies define the composition of human ESCRT-1 complexes and indicate that the MVB12 subunits play a unique role in regulating ESCRT-mediated virus budding.