Crystallographic and functional analysis of the ESCRT-I /HIV-1 Gag PTAP interaction.
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Im YJ, Kuo L, Ren X, Burgos PV, Zhao XZ, Liu F, Burke TR Jr, Bonifacino JS, Freed EO, Hurley JH
Crystallographic and functional analysis of the ESCRT-I /HIV-1 Gag PTAP interaction.
Structure. 2010 Nov 10;18(11):1536-47. doi: 10.1016/j.str.2010.08.010.
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- 21070952 [ View in PubMed]
- 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 A 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.