期刊
SCIENCE
卷 341, 期 6152, 页码 1387-1390出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1241475
关键词
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资金
- National Basic Research Program of China [2012CB518000, 2012CB910400]
- NIH [R01 AI100604, U54 GM094618]
- National Science Foundation of China [31270766, 81161120425, 81025017]
- Shanghai Science and Technology Committee [11JC1414800, 12PJ1410500]
- [U01 GM094612]
- [R01 GM071872]
The CCR5 chemokine receptor acts as a co-receptor for HIV-1 viral entry. Here we report the 2.7 angstrom-resolution crystal structure of human CCR5 bound to the marketed HIV drug maraviroc. The structure reveals a ligand-binding site that is distinct from the proposed major recognition sites for chemokines and the viral glycoprotein gp120, providing insights into the mechanism of allosteric inhibition of chemokine signaling and viral entry. A comparison between CCR5 and CXCR4 crystal structures, along with models of co-receptor-gp120-V3 complexes, suggests that different charge distributions and steric hindrances caused by residue substitutions may be major determinants of HIV-1 co-receptor selectivity. These high-resolution insights into CCR5 can enable structure-based drug discovery for the treatment of HIV-1 infection.
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