4MBS

Crystal Structure of the CCR5 Chemokine Receptor

Summary for 4MBS

• Entry DOI: 10.2210/pdb4mbs/pdb
• Descriptor: Chimera protein of C-C chemokine receptor type 5 and Rubredoxin, 4,4-difluoro-N-[(1S)-3-{(3-exo)-3-[3-methyl-5-(propan-2-yl)-4H-1,2,4-triazol-4-yl]-8-azabicyclo[3.2.1]oct-8-yl}-1-phenylpropyl]cyclohexanecarboxamide, ZINC ION, ... (5 entities in total)
• Functional Keywords: human ccr5 chemokine receptor, anti-hiv agent, novel protein engineering, gpcr network, membrane protein, psi-biology, structural genomics, seven transmembrane helices, g protein-coupled receptor, membrane, signaling protein
• Biological source: Homo sapiens; More
• Cellular location: Cell membrane ; Multi-pass membrane protein : P51681
• Total number of polymer chains: 2
• Total formula weight: 99756.11

Authors

Tan, Q.,Zhu, Y.,Han, G.W.,Li, J.,Fenalti, G.,Liu, H.,Cherezov, V.,Stevens, R.C.,GPCR Network (GPCR),Zhao, Q.,Wu, B. (deposition date: 2013-08-19, release date: 2013-09-11, Last modification date: 2023-09-20)

Primary citation

Tan, Q.,Zhu, Y.,Li, J.,Chen, Z.,Han, G.W.,Kufareva, I.,Li, T.,Ma, L.,Fenalti, G.,Li, J.,Zhang, W.,Xie, X.,Yang, H.,Jiang, H.,Cherezov, V.,Liu, H.,Stevens, R.C.,Zhao, Q.,Wu, B.
Structure of the CCR5 chemokine receptor-HIV entry inhibitor maraviroc complex.
Science, 341:1387-1390, 2013

PubMed Abstract: 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.

PubMed: 24030490
DOI: 10.1126/science.1241475

Experimental method

X-RAY DIFFRACTION (2.71 Å)