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

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[21] HIV-1 Env trimers asymmetrically engage CD4 receptors in membranes [J].

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Qin, Zhuan ;

Nand, Elizabeth ;

Grunst, Michael W. ;

Grover, Jonathan R. ;

Bess, Julian W., Jr. ;

Lifson, Jeffrey D. ;

Zwick, Michael B. ;

Tagare, Hemant D. ;

Uchil, Pradeep D. ;

Mothes, Walther .

NATURE, 2023, 623 (7989) :1026-+

[22] Quaternary Interaction of the HIV-1 Envelope Trimer with CD4 and Neutralizing Antibodies [J].

Liu, Qingbo ;

Zhang, Peng ;

Lusso, Paolo .

VIRUSES-BASEL, 2021, 13 (07)

[23] Quaternary contact in the initial interaction of CD4 with the HIV-1 envelope trimer [J].

Liu, Qingbo ;

Acharya, Priyamvada ;

Dolan, Michael A. ;

Zhang, Peng ;

Guzzo, Christina ;

Lu, Jacky ;

Kwon, Alice ;

Gururani, Deepali ;

Miao, Huiyi ;

Bylund, Tatsiana ;

Chuang, Gwo-Yu ;

Druz, Aliaksandr ;

Zhou, Tongqing ;

Rice, William J. ;

Wigge, Christoph ;

Carragher, Bridget ;

Potter, Clinton S. ;

Kwong, Peter D. ;

Lusso, Paolo .

NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2017, 24 (04) :370-+

[24] The adaptor molecule CD2AP in CD4 T cells modulates differentiation of follicular helper T cells during chronic LCMV infection [J].

Raju, Saravanan ;

Kometani, Kohei ;

Kurosaki, Tomohiro ;

Shaw, Andrey S. ;

Egawa, Takeshi .

PLOS PATHOGENS, 2018, 14 (05)

[25] HIV-1 Env and Nef Cooperatively Contribute to Plasmacytoid Dendritic Cell Activation via CD4-Dependent Mechanisms [J].

Reszka-Blanco, Natalia J. ;

Sivaraman, Vijay ;

Zhang, Liguo ;

Su, Lishan .

JOURNAL OF VIROLOGY, 2015, 89 (15) :7604-7611

[26] Molecular insights into the inhibition of HIV-1 infection using a CD4 domain-1-specific monoclonal antibody [J].

Hou, Wangheng ;

Fang, Chu ;

Liu, Jiayan ;

Yu, Hai ;

Qi, Jialong ;

Zhang, Zhiqing ;

Yuan, Ruixue ;

Xiong, Dan ;

Gao, Shuangquan ;

Yuan, Y. Adam ;

Li, Shaowei ;

Gu, Ying ;

Xia, Ningshao .

ANTIVIRAL RESEARCH, 2015, 122 :101-111

[27] The landscape of alternative splicing in HIV-1 infected CD4 T-cells [J].

Byun, Seyoun ;

Han, Seonggyun ;

Zheng, Yue ;

Planelles, Vicente ;

Lee, Younghee .

BMC MEDICAL GENOMICS, 2020, 13 (Suppl 5)

[28] Prestimulation of CD2 confers resistance to HIV-1 latent infection in blood resting CD4 T cells [J].

He, Sijia ;

Guo, Jia ;

Fu, Yajing ;

Spear, Mark ;

Qin, Chaolong ;

Fu, Shuai ;

Cui, Zongqiang ;

Jin, Wenwen ;

Xu, Xuehua ;

Chen, Wanjun ;

Shang, Hong ;

Wu, Yuntao .

ISCIENCE, 2021, 24 (11)

[29] Engineering and exploitation of a fluorescent HIV-1 gp120 for live cell CD4 binding assays [J].

Costantini, Lindsey M. ;

Irvin, Susan C. ;

Kennedy, Steven C. ;

Guo, Feng ;

Goldstein, Harris ;

Herold, Betsy C. ;

Snapp, Erik L. .

VIROLOGY, 2015, 476 :240-248

[30] Amino acids at positions 3, 168, and 169 are associated with the ability of Nef proteins from HIV-1 CRF01_AE to downmodulate CD4 [J].

Kuang, Wen-Dong ;

Zhou, Yan-Heng ;

Zhong, Ping ;

Zhang, Chiyu ;

Wang, Jian-Hua .

JOURNAL OF MEDICAL VIROLOGY, 2017, 89 (10) :1788-1795

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