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

被引：60

作者：

Im, Young Jun ^{[1
]}

Kuo, Lillian ^{[2
]}

Ren, Xuefeng ^{[1
]}

Burgos, Patricia V. ^{[3
]}

Zhao, Xue Zhi ^{[4
]}

Liu, Fa ^{[4
]}

Burke, Terrence R., Jr. ^{[4
]}

Bonifacino, Juan S. ^{[3
]}

Freed, Eric O. ^{[2
]}

Hurley, James H. ^{[1
]}

机构：

[1] NIDDK, Mol Biol Lab, NIH, Bethesda, MD 20892 USA

[2] NCI, HIV Drug Resistance Program, CCR, Frederick, MD 21702 USA

[3] Eunice Kennedy Shriver Natl Inst Child Hlth & Dev, Cell Biol & Metab Program, NIH, Bethesda, MD 20892 USA

[4] NCI, Biol Chem Lab, Mol Discovery Program, CCR, Frederick, MD 21702 USA

来源：

STRUCTURE | 2010年 / 18卷 / 11期

关键词：

TRANSPORT ESCRT-I; PEPTIDE MOTIFS; LATE DOMAIN; TSG101; PROTEIN; MUTATIONS; COMPLEX; MACHINERY; UBIQUITIN; IDENTIFICATION;

D O I：

10.1016/j.str.2010.08.010

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：1536 / 1547

页数：12

共 47 条

[41] Inhibition of HIV Budding by a Genetically Selected Cyclic Peptide Targeting the Gag-TSG101 Interaction [J].