3OBX

Crystal structure of the Tsg101 UEV domain in complex with a HIV-1 Gag P7A mutant peptide

Summary for 3OBX

• Entry DOI: 10.2210/pdb3obx/pdb
• Related: 3OBQ 3OBS 3OBU
• Descriptor: Tumor susceptibility gene 101 protein, Gag polyprotein (3 entities in total)
• Functional Keywords: protein tranport, ubiquitin, hiv-1 gag, protein transport
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm: Q99816; Matrix protein p17: Virion (By similarity): Q72497
• Total number of polymer chains: 2
• Total formula weight: 17441.15

Authors

Im, Y.J.,Hurley, J.H. (deposition date: 2010-08-09, release date: 2010-12-01, Last modification date: 2023-09-06)

Primary citation

Im, Y.J.,Kuo, L.,Ren, X.,Burgos, P.V.,Zhao, X.Z.,Liu, F.,Burke, T.R.,Bonifacino, J.S.,Freed, E.O.,Hurley, J.H.
Crystallographic and Functional Analysis of the ESCRT-I /HIV-1 Gag PTAP Interaction.
Structure, 18:1536-1547, 2010

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 Å 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.

PubMed: 21070952
DOI: 10.1016/j.str.2010.08.010

Experimental method

X-RAY DIFFRACTION (1.6 Å)