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Crystallographic and Functional Analysis of the ESCRT-I/HIV-1 Gag PTAP Interaction

  1. Author:
    Im, Y. J.
    Kuo, L.
    Ren, X. F.
    Burgos, P. V.
    Zhao, X. Z.
    Liu, F.
    Burke, T. R.
    Bonifacino, J. S.
    Freed, E. O.
    Hurley, J. H.

  2. Author Address

    [Im, Young Jun; Ren, Xuefeng; Hurley, James H.] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. [Kuo, Lillian; Freed, Eric O.] NCI, HIV Drug Resistance Program, CCR, Frederick, MD 21702 USA. [Burgos, Patricia V.; Bonifacino, Juan S.] Eunice Kennedy Shriver Natl Inst Child Hlth & Dev, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA. [Zhao, Xue Zhi; Liu, Fa; Burke, Terrence R., Jr.] NCI, Biol Chem Lab, Mol Discovery Program, CCR, Frederick, MD 21702 USA.;Hurley, JH, NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA.;hurley@helix.nih.gov
    1. Year: 2010
    2. Date: Nov
  2. Journal: Structure
    1. 18
    2. 11
    3. Pages: 1536-1547
  4. Type of Article: Article
  5. ISSN: 0969-2126
  1. Abstract:

    Budding of HIV-1 requires the binding of the PTAP late domain of the Gag p6 protein to the UEV domain of the TSG101 subunit of ESCRT-I. The normal function of this motif in cells is in receptor downregulation. Here, we report the 1.4-1.6 angstrom structures of the human TSG101 UEV domain alone and with wild-type and mutant HIV-1 PTAP and Hrs PSAP nonapeptides. The hydroxyl of the Thr or Ser residue in the P(S/T)AP motif hydrogen bonds with the main chain of Asn69. Mutation of the Asn to Pro, blocking the main-chain amide, abrogates PTAP motif binding in vitro and blocks budding of HIV-1 from cells. N69P and other PTAP binding-deficient alleles of TSG101 did not rescue HIV-1 budding. However, the mutant alleles did rescue downregulation of endogenous EGF receptor. This demonstrates that the PSAP motif is not rate determining in EGF receptor downregulation under normal conditions.

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External Sources

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  2. DOI: 10.1016/j.str.2010.08.010
  3. View record in Web of Science®
  4. WOS: 000284435100017

Library Notes

  1. Fiscal Year: FY2010-2011
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