期刊
CELL HOST & MICROBE
卷 2, 期 1, 页码 41-53出版社
CELL PRESS
DOI: 10.1016/j.chom.2007.06.003
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资金
- NIAID NIH HHS [R01 AI051174-02, R37 AI051174, R01 AI051174, AI051174] Funding Source: Medline
- NIGMS NIH HHS [P50 GM082545] Funding Source: Medline
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.
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