4RWS

Crystal structure of CXCR4 and viral chemokine antagonist vMIP-II complex (PSI Community Target)

Summary for 4RWS

• Entry DOI: 10.2210/pdb4rws/pdb
• Related: 3ODU 3OE0 3OE6 3OE8 3OE9
• Descriptor: C-X-C chemokine receptor type 4/Endolysin chimeric protein, Viral macrophage inflammatory protein 2 (2 entities in total)
• Functional Keywords: human chemokine-chemokine receptor complex, gpcr signaling, psi-biology, gpcr network, membrane protein, gpcr, cxcr4, viral antagonist chemokine vmip-ii, membrane, lipidic cubic phase, t4l, structural genomics, signaling protein, hydrolase
• Biological source: Homo sapiens; More
• Cellular location: Cell membrane; Multi-pass membrane protein: P61073; Secreted: Q98157
• Total number of polymer chains: 2
• Total formula weight: 65746.21

Authors

Qin, L.,Kufareva, I.,Holden, L.,Wang, C.,Zheng, Y.,Wu, H.,Fenalti, G.,Han, G.W.,Cherezov, V.,Abagyan, R.,Stevens, R.C.,Handel, T.M.,GPCR Network (GPCR) (deposition date: 2014-12-05, release date: 2015-02-11, Last modification date: 2023-09-20)

Primary citation

Qin, L.,Kufareva, I.,Holden, L.G.,Wang, C.,Zheng, Y.,Zhao, C.,Fenalti, G.,Wu, H.,Han, G.W.,Cherezov, V.,Abagyan, R.,Stevens, R.C.,Handel, T.M.
Structural biology. Crystal structure of the chemokine receptor CXCR4 in complex with a viral chemokine.
Science, 347:1117-1122, 2015

PubMed Abstract: 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.

PubMed: 25612609
DOI: 10.1126/science.1261064

Experimental method

X-RAY DIFFRACTION (3.1 Å)