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 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.
Morita
Eiji
E
Department of Biochemistry, University of Utah, Salt Lake City, UT 84112-5650, USA.
Sandrin
Virginie
V
Alam
Steven L
SL
Eckert
Debra M
DM
Gygi
Steven P
SP
Sundquist
Wesley I
WI
D001692:Biological Transport; D056827:Endosomal Sorting Complexes Required for Transport; D011992:Endosomes / Q000382:microbiology / Q000502:physiology; D015497:HIV-1 / Q000254:growth & development*; D006801:Humans; D009024:Morphogenesis; D021122:Protein Subunits / Q000502:physiology; D011956:Receptors, Cell Surface; D029701:Saccharomyces cerevisiae Proteins / Q000502:physiology
D056827:Endosomal Sorting Complexes Required for Transport; C517100:Mvb12 protein, S cerevisiae; D021122:Protein Subunits; D011956:Receptors, Cell Surface; D029701:Saccharomyces cerevisiae Proteins