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

[31] CD4 Incorporation into HIV-1 Viral Particles Exposes Envelope Epitopes Recognized by CD4-Induced Antibodies [J].

Ding, Shilei ;

Gasser, Romain ;

Gendron-Lepage, Gabrielle ;

Medjahed, Halima ;

Tolbert, William D. ;

Sodroski, Joseph ;

Pazgier, Marzena ;

Finzi, Andres .

JOURNAL OF VIROLOGY, 2019, 93 (22)

[32] Study on molecular mechanisms of CD4 dependency and independency of HIV-1 gp120 [J].

Liu, Meng-Ting ;

Shen, Jian-Xin ;

Li, Xin-Wei ;

Yang, Li ;

Li, Yi ;

Sang, Peng ;

Yang, Li-Quan .

RSC ADVANCES, 2023, 13 (09) :6274-6286

[33] CD4 Expression and Env Conformation Are Critical for HIV-1 Restriction by SERINC5 [J].

Zhang, Xihe ;

Shi, Jing ;

Qiu, Xusheng ;

Chai, Qingqing ;

Frabutt, Dylan A. ;

Schwartz, Richard C. ;

Zheng, Yong-Hui .

JOURNAL OF VIROLOGY, 2019, 93 (14)

[34] Fluorescent CD4 probe for potential HIV-1 gp120 protein detection [J].

Wang, Zhongjie ;

Talukder, Poulami ;

Hecht, Sidney M. ;

Chen, Shengxi .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2015, 25 (06) :1182-1185

[35] IL-7 and CD4 T Follicular Helper Cells in HIV-1 Infection [J].

Chiodi, Francesca ;

Bekele, Yonas ;

Graham, Rebecka Lantto ;

Nasi, Aikaterini .

FRONTIERS IN IMMUNOLOGY, 2017, 8

[36] Conformational Engineering of HIV-1 Env Based on Mutational Tolerance in the CD4 and PG16 Bound States [J].

Heredia, Jeremiah D. ;

Park, Jihye ;

Choi, Hannah ;

Gill, Kevin S. ;

Procko, Erik .

JOURNAL OF VIROLOGY, 2019, 93 (11)

[37] Conformation of HIV-1 Envelope Governs Rhesus CD4 Usage and Simian-Human Immunodeficiency Virus Replication [J].

Vilmen, Geraldine ;

Smith, Anna C. ;

Benet, Hector Cervera ;

Shukla, Rajni Kant ;

Larue, Ross C. ;

Herschhorn, Alon ;

Sharma, Amit .

MBIO, 2022, 13 (01)

[38] PLA2G1B is involved in CD4 anergy and CD4 lymphopenia in HIV-infected patients [J].

Pothlichet, Julien ;

Rose, Thierry ;

Bugault, Florence ;

Jeammet, Louise ;

Meola, Annalisa ;

Haouz, Ahmed ;

Saul, Frederick ;

Geny, David ;

Alcami, Jose ;

Ruiz-Mateos, Ezequiel ;

Teyton, Luc ;

Lambeau, Gerard ;

Theze, Jacques .

JOURNAL OF CLINICAL INVESTIGATION, 2020, 130 (06) :2872-2887

[39] Differential Vpu-Mediated CD4 and Tetherin Downregulation Functions among Major HIV-1 Group M Subtypes [J].

Umviligihozo, Gisele ;

Cobarrubias, Kyle D. ;

Chandrarathna, Sandali ;

Jin, Steven W. ;

Reddy, Nicole ;

Byakwaga, Helen ;

Muzoora, Conrad ;

Bwana, Mwebesa B. ;

Lee, Guinevere Q. ;

Hunt, Peter W. ;

Martin, Jeff N. ;

Brumme, Chanson J. ;

Bangsberg, David R. ;

Karita, Etienne ;

Allen, Susan ;

Hunter, Eric ;

Ndung'u, Thumbi ;

Brumme, Zabrina L. ;

Brockman, Mark A. .

JOURNAL OF VIROLOGY, 2020, 94 (14)

[40] Nanoparticles presenting clusters of CD4 expose a universal vulnerability of HIV-1 by mimicking target cells [J].

Hoffmann, Magnus A. G. ;

Bar-On, Yotam ;

Yang, Zhi ;

Gristick, Harry B. ;

Gnanapragasam, Priyanthi N. P. ;

Vielmetter, Jost ;

Nussenzweig, Michel C. ;

Bjorkman, Pamela J. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2020, 117 (31) :18719-18728

← 1 2 3 4 5 →