3obu

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Crystal structure of the Tsg101 UEV domain in complex with a HIV-1 PTAP peptide

Structural highlights

3obu is a 2 chain structure with sequence from Homo sapiens and Human immunodeficiency virus 1. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.6Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

TS101_HUMAN Component of the ESCRT-I complex, a regulator of vesicular trafficking process. Binds to ubiquitinated cargo proteins and is required for the sorting of endocytic ubiquitinated cargos into multivesicular bodies (MVBs). Mediates the association between the ESCRT-0 and ESCRT-I complex. Required for completion of cytokinesis; the function requires CEP55. May be involved in cell growth and differentiation. Acts as a negative growth regulator. Involved in the budding of many viruses through an interaction with viral proteins that contain a late-budding motif P-[ST]-A-P. This interaction is essential for viral particle budding of numerous retroviruses.^[1] ^[2] ^[3]

Publication Abstract from PubMed

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.

Crystallographic and functional analysis of the ESCRT-I /HIV-1 Gag PTAP interaction.,Im YJ, Kuo L, Ren X, Burgos PV, Zhao XZ, Liu F, Burke TR Jr, Bonifacino JS, Freed EO, Hurley JH Structure. 2010 Nov 10;18(11):1536-47. PMID:21070952^[4]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Bishop N, Horman A, Woodman P. Mammalian class E vps proteins recognize ubiquitin and act in the removal of endosomal protein-ubiquitin conjugates. J Cell Biol. 2002 Apr 1;157(1):91-101. Epub 2002 Mar 26. PMID:11916981 doi:10.1083/jcb.200112080
↑ Morita E, Sandrin V, Chung HY, Morham SG, Gygi SP, Rodesch CK, Sundquist WI. Human ESCRT and ALIX proteins interact with proteins of the midbody and function in cytokinesis. EMBO J. 2007 Oct 3;26(19):4215-27. Epub 2007 Sep 13. PMID:17853893 doi:10.1038/sj.emboj.7601850
↑ Carlton JG, Martin-Serrano J. Parallels between cytokinesis and retroviral budding: a role for the ESCRT machinery. Science. 2007 Jun 29;316(5833):1908-12. Epub 2007 Jun 7. PMID:17556548 doi:10.1126/science.1143422
↑ 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. PMID:21070952 doi:10.1016/j.str.2010.08.010