3OBQ: Crystal Structure Of The Tsg101 Uev Domain In Complex With A Human Hrs Psap Peptide

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.
PDB ID: 3OBQDownload
MMDB ID: 86628
PDB Deposition Date: 2010/8/9
Updated in MMDB: 2010/12
Experimental Method:
x-ray diffraction
Resolution: 1.4  Å
Source Organism:
Similar Structures:
Biological Unit for 3OBQ: dimeric; determined by author and by software (PISA)
Molecular Components in 3OBQ
Label Count Molecule
Proteins (2 molecules)
Tumor Susceptibility Gene 101 Protein(Gene symbol: TSG101)
Molecule annotation
Hepatocyte Growth Factor-regulated Tyrosine Kinase Substrate(Gene symbol: HGS)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB