Identification of human VPS37C, a component of endosomal sorting complex required for transport-I important for viral budding.
Endosomal sorting complex required for transport-I (ESCRT-I) is one of three defined protein complexes in the class E vacuolar protein sorting (VPS) pathway required for the sorting of ubiquitinated transmembrane proteins into internal vesicles of multivesicular bodies. In yeast, ESCRT-I is composed of three proteins, VSP23, VPS28, and VPS37, whereas ... in mammals only Tsg101(VPS23) and VPS28 were originally identified as ESCRT-I components. Using yeast two-hybrid screens, we identified one of a family of human proteins (VPS37C) as a Tsg101-binding protein. VPS37C can form a ternary complex with Tsg101 and VPS28 by binding to a domain situated toward the carboxyl terminus of Tsg101 and binds to another class E VPS factor, namely Hrs. In addition, VPS37C is recruited to aberrant endosomes induced by overexpression of Tsg101, Hrs, or dominant negative form of the class E VPS ATPase, VPS4. Enveloped viruses that encode PTAP motifs to facilitate budding exploit ESCRT-I as an interface with the class E VPS pathway, and accordingly, VPS37C is recruited to the plasma membrane along with Tsg101 by human immunodeficiency virus, type 1 (HIV-1) Gag. Moreover, direct fusion of VPS37C to HIV-1 Gag obviates the requirement for a PTAP motif to induce virion release. Depletion of VPS37C from cells does not inhibit murine leukemia virus budding, which is not mediated by ESCRT-I, however, if murine leukemia virus budding is engineered to be ESCRT-I-dependent, then it is inhibited by VPS37C depletion, and this inhibition is accentuated if VPS37B is simultaneously depleted. Thus, this study identifies VPS37C as a functional component of mammalian ESCRT-I.
Mesh Terms:
Amino Acid Sequence, Cell Line, Cytoplasmic Vesicles, DNA-Binding Proteins, Endosomal Sorting Complexes Required for Transport, Gene Products, gag, HIV Infections, HIV-1, Humans, Leukemia Virus, Murine, Molecular Sequence Data, Multiprotein Complexes, Protein Binding, Protein Structure, Tertiary, Protein Transport, Transcription Factors, Vesicular Transport Proteins, Virus Replication
Amino Acid Sequence, Cell Line, Cytoplasmic Vesicles, DNA-Binding Proteins, Endosomal Sorting Complexes Required for Transport, Gene Products, gag, HIV Infections, HIV-1, Humans, Leukemia Virus, Murine, Molecular Sequence Data, Multiprotein Complexes, Protein Binding, Protein Structure, Tertiary, Protein Transport, Transcription Factors, Vesicular Transport Proteins, Virus Replication
J. Biol. Chem.
Date: Jan. 07, 2005
PubMed ID: 15509564
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