Structural basis for viral late-domain binding to Alix

被引：127

作者：

Lee, Sangho

Joshi, Anjali

Nagashima, Kunio

Freed, Eric O.

Hurley, James H. ^{[1
]}

机构：

[1] NIDDK, Mol Biol Lab, NIH, US Dept Hlth & Human Serv, Bethesda, MD 20892 USA

[2] NCI, Virus Cell Interact Sect, HIV Drug Resistance Program, NIH,US Dept Hlth & Human Serv, Frederick, MD 21702 USA

[3] NCI, Image Anal Lab, Res Technol Program, SAIC Frederick,NIH,US Dept Hlth & Human Serv, Frederick, MD 21702 USA

来源：

NATURE STRUCTURAL & MOLECULAR BIOLOGY | 2007年 / 14卷 / 03期

关键词：

D O I：

10.1038/nsmb1203

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：

The modular protein Alix is a central node in endosomal-lysosomal trafficking and the budding of human immunodeficiency virus (HIV)-1. The Gag p6 protein of HIV-1 contains a LYPx(n)LxxL motif that is required for Alix-mediated budding and binds a region of Alix spanning residues 360-702. The structure of this fragment of Alix has the shape of the letter 'V' and is termed the V domain. The V domain has a topologically complex arrangement of 11 alpha-helices, with connecting loops that cross three times between the two arms of the V. The conserved residue Phe676 is at the center of a large hydrophobic pocket and is crucial for binding to a peptide model of HIV-1 p6. Overexpression of the V domain inhibits HIV-1 release from cells. This inhibition of release is reversed by mutations that block binding of the Alix V domain to p6.

引用

页码：194 / 199

页数：6

共 45 条

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