Identification of human MVB12 proteins as ESCRT-I subunits that function in HIV budding

Human ESCRT-I is a multiprotein complex that plays essential roles in HIV budding and endosomal protein sorting. All ESCRT-I complexes contain three common subunits (TSG101, VPS28, and VPS37), and a fourth subunit of yeast ESCRT-I was recently identified (Mvb12p). We now demonstrate that two related...

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Bibliographic Details
Published in:Cell host & microbe 2007-07, Vol.2 (1), p.41-53
Main Authors: Morita, Eiji, Sandrin, Virginie, Alam, Steven L, Eckert, Debra M, Gygi, Steven P, Sundquist, Wesley I
Format: Article
Language:English
Subjects:
Biological Transport
Endosomal Sorting Complexes Required for Transport
Endosomes - microbiology
Endosomes - physiology
HIV-1 - growth & development
Humans
Morphogenesis
Protein Subunits - physiology
Receptors, Cell Surface
Saccharomyces cerevisiae Proteins - physiology
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Summary:Human ESCRT-I is a multiprotein complex that plays essential roles in HIV budding and endosomal protein sorting. All ESCRT-I complexes contain three common subunits (TSG101, VPS28, and VPS37), and a fourth subunit of yeast ESCRT-I was recently identified (Mvb12p). We now demonstrate that two related human proteins (MVB12A and MVB12B) constitute the fourth class of metazoan ESCRT-I subunits, despite lacking identifiable sequence homology to Mvb12p. Hydrodynamic studies indicate that soluble human ESCRT-I 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-I complexes and indicate that the MVB12 subunits play a unique role in regulating ESCRT-mediated virus budding.
ISSN:1931-3128
1934-6069
DOI:10.1016/j.chom.2007.06.003