How HIV-1 Nef hijacks the AP-2 clathrin adaptor to downregulate CD4

被引：92

作者：

Ren, Xuefeng ^{[1
,2
,3
]}

Park, Sang Yoon ^{[3
]}

Bonifacino, Juan S. ^{[3
]}

Hurley, James H. ^{[1
,2
]}

机构：

[1] Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA

[2] Univ Calif Berkeley, Calif Inst Quantit Biosci, Berkeley, CA 94720 USA

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

来源：

ELIFE | 2014年 / 3卷

基金：

美国国家卫生研究院;

关键词：

VIRUS TYPE-1 NEF; CELL-SURFACE CD4; DILEUCINE MOTIF; CRYSTAL-STRUCTURE; STRUCTURAL BASIS; BINDING SURFACE; SH3; DOMAIN; PROTEIN; EXPRESSION; IDENTIFICATION;

D O I：

10.7554/eLife.01754

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The Nef protein of HIV-1 downregulates the cell surface co-receptor CD4 by hijacking the clathrin adaptor complex AP-2. The structural basis for the hijacking of AP-2 by Nef is revealed by a 2.9 angstrom crystal structure of Nef bound to the a and sigma 2 subunits of AP-2. Nef binds to AP-2 via its central loop (residues 149-179) and its core. The determinants for Nef binding include residues that directly contact AP-2 and others that stabilize the binding-competent conformation of the central loop. Residues involved in both direct and indirect interactions are required for the binding of Nef to AP-2 and for downregulation of CD4. These results lead to a model for the docking of the full AP-2 tetramer to membranes as bound to Nef, such that the cytosolic tail of CD4 is situated to interact with its binding site on Nef.

引用

页数：19

共 50 条

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