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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.

Pubmed ID: 15509564

Authors

  • Eastman SW
  • Martin-Serrano J
  • Chung W
  • Zang T
  • Bieniasz PD

Journal

The Journal of biological chemistry

Publication Data

January 7, 2005

Associated Grants

  • Agency: NIAID NIH HHS, Id: R01-AI052774

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