Crystal structure of the chemokine receptor CXCR4 in complex with a viral chemokine

被引：300

作者：

Qin, Ling ^{[1
]}

Kufareva, Irina ^{[1
]}

Holden, Lauren G. ^{[1
]}

Wang, Chong ^{[2
]}

Zheng, Yi ^{[1
]}

Zhao, Chunxia ^{[1
]}

Fenalti, Gustavo ^{[2
]}

Wu, Huixian ^{[2
]}

Han, Gye Won ^{[3
,4
]}

Cherezov, Vadim ^{[3
]}

Abagyan, Ruben ^{[1
]}

Stevens, Raymond C. ^{[3
,4
]}

Handel, Tracy M. ^{[1
]}

机构：

[1] Univ Calif San Diego, Skaggs Sch Pharm & Pharmaceut Sci, La Jolla, CA 92093 USA

[2] Scripps Res Inst, Dept Integrat Struct & Computat Biol, La Jolla, CA 92037 USA

[3] Univ So Calif, Bridge Inst, Dept Chem, Los Angeles, CA 90089 USA

[4] Univ So Calif, Bridge Inst, Dept Biol Sci, Los Angeles, CA 90089 USA

来源：

SCIENCE | 2015年 / 347卷 / 6226期

基金：

美国国家卫生研究院;

关键词：

IMMUNODEFICIENCY-VIRUS TYPE-1; CELL-DERIVED FACTOR-1-ALPHA; VMIP-II; SULFOTYROSINE RECOGNITION; SMALL-MOLECULE; CC-CHEMOKINE; BINDING; HIV-1; LYMPHOPOIESIS; MYELOPOIESIS;

D O I：

10.1126/science.1261064

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Chemokines and their receptors control cell migration during development, immune system responses, and in numerous diseases, including inflammation and cancer. The structural basis of receptor: chemokine recognition has been a long-standing unanswered question due to the challenges of structure determination for membrane protein complexes. Here, we report the crystal structure of the chemokine receptor CXCR4 in complex with the viral chemokine antagonist vMIP-II at 3.1 angstrom resolution. The structure revealed a 1: 1 stoichiometry and a more extensive binding interface than anticipated from the paradigmatic two-site model. The structure helped rationalize a large body of mutagenesis data and together with modeling provided insights into CXCR4 interactions with its endogenous ligand CXCL12, its ability to recognize diverse ligands, and the specificity of CC and CXC receptors for their respective chemokines.

引用

页码：1117 / 1122

页数：6

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