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

• Published in: Cell host & microbe Vol. 2; no. 1; pp. 41 - 53
• Main Authors: Morita, Eiji, Sandrin, Virginie, Alam, Steven L, Eckert, Debra M, Gygi, Steven P, Sundquist, Wesley I
• Format: Journal Article
• Language: English
• Published: United States 12.07.2007
• 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
• ISSN: 1931-3128; 1934-6069
• DOI: 10.1016/j.chom.2007.06.003

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.