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

[41] Engineered Single Human CD4 Domains as Potent HIV-1 Inhibitors and Components of Vaccine Immunogens [J].

Chen, Weizao ;

Feng, Yang ;

Gong, Rui ;

Zhu, Zhongyu ;

Wang, Yanping ;

Zhao, Qi ;

Dimitrov, Dimiter S. .

JOURNAL OF VIROLOGY, 2011, 85 (18) :9395-9405

[42] Atlas of the HIV-1 Reservoir in Peripheral CD4 T Cells of Individuals on Successful Antiretroviral Therapy [J].

Galvez, Cristina ;

Grau-Exposito, Judith ;

Urrea, Victor ;

Clotet, Bonaventura ;

Falco, Vicenc ;

Buzon, Maria Jose ;

Martinez-Picado, Javier .

MBIO, 2021, 12 (06)

[43] HIV-1 Vpr inhibits autophagy during the early steps of infection of CD4 T cells [J].

Alfaisal, Jamal ;

Machado, Alice ;

Galais, Mathilde ;

Robert-Hebmann, Veronique ;

Arnaune-Pelloquin, Laetitia ;

Espert, Lucile ;

Biard-Piechaczyk, Martine .

BIOLOGY OF THE CELL, 2019, 111 (12) :308-318

[44] Transcriptional Profiling of CD4 T Cells Identifies Distinct Subgroups of HIV-1 Elite Controllers [J].

Vigneault, Francois ;

Woods, Matthew ;

Buzon, Maria J. ;

Li, Chun ;

Pereyra, Florencia ;

Crosby, Seth D. ;

Rychert, Jennifer ;

Church, George ;

Martinez-Picado, Javier ;

Rosenberg, Eric S. ;

Telenti, Amalio ;

Yu, Xu G. ;

Lichterfeld, Mathias .

JOURNAL OF VIROLOGY, 2011, 85 (06) :3015-3019

[45] Structural Basis of Immune Evasion at the Site of CD4 Attachment on HIV-1 gp120 [J].

Chen, Lei ;

Kwon, Young Do ;

Zhou, Tongqing ;

Wu, Xueling ;

O'Dell, Sijy ;

Cavacini, Lisa ;

Hessell, Ann J. ;

Pancera, Marie ;

Tang, Min ;

Xu, Ling ;

Yang, Zhi-Yong ;

Zhang, Mei-Yun ;

Arthos, James ;

Burton, Dennis R. ;

Dimitrov, Dimiter S. ;

Nabel, Gary J. ;

Posner, Marshall R. ;

Sodroski, Joseph ;

Wyatt, Richard ;

Mascola, John R. ;

Kwong, Peter D. .

SCIENCE, 2009, 326 (5956) :1123-1127

[46] Vpu Augments the Initial Burst Phase of HIV-1 Propagation and Downregulates BST2 and CD4 in Humanized Mice [J].

Sato, Kei ;

Misawa, Naoko ;

Fukuhara, Mitsuko ;

Iwami, Shingo ;

An, Dong Sung ;

Ito, Mamoru ;

Koyanagi, Yoshio .

JOURNAL OF VIROLOGY, 2012, 86 (09) :5000-5013

[47] Thermal Stability of the Human Immunodeficiency Virus Type 1 (HIV-1) Receptors, CD4 and CXCR4, Reconstituted in Proteoliposomes [J].

Zhukovsky, Mikhail A. ;

Basmaciogullari, Stephane ;

Pacheco, Beatriz ;

Wang, Liping ;

Madani, Navid ;

Haim, Hillel ;

Sodroski, Joseph .

PLOS ONE, 2010, 5 (10)

[48] No detectable differences in Nef-mediated downregulation of HLA-I and CD4 molecules among HIV-1 group M lineages circulating in Cameroon, where the pandemic originated [J].

Sonela, Nelson ;

Mann, Jaclyn ;

Godwe, Celestin ;

Goni, Oumarou H. ;

Tchakoute, Merime ;

Nkoue, Nathalie ;

de Oliveira, Tulio ;

Brockman, Mark A. ;

Brumme, Zabrina L. ;

Ndung'u, Thumbi ;

Tongo, Marcel .

FRONTIERS IN VIROLOGY, 2024, 4

[49] A Basic Patch on α-Adaptin Is Required for Binding of Human Immunodeficiency Virus Type 1 Nef and Cooperative Assembly of a CD4-Nef-AP-2 Complex [J].

Chaudhuri, Rittik ;

Mattera, Rafael ;

Lindwasser, O. Wolf ;

Robinson, Margaret S. ;

Bonifacino, Juan S. .

JOURNAL OF VIROLOGY, 2009, 83 (06) :2518-2530

[50] Molecular and Genetic Characterization of Natural Variants of HIV-1 Nef Gene from North India and its Functional Implication in Down-Regulation of MHC-I and CD-4 [J].

Singh, J. ;

Ronsard, L. ;

Pandey, M. ;

Kapoor, R. ;

Ramachandran, V. G. ;

Banerjea, A. C. .

CURRENT HIV RESEARCH, 2021, 19 (02) :172-187

← 1 2 3 4 5 →