Research ArticleBiochemistry

Key determinants of selective binding and activation by the monocyte chemoattractant proteins at the chemokine receptor CCR2

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Science Signaling  23 May 2017:
Vol. 10, Issue 480, eaai8529
DOI: 10.1126/scisignal.aai8529

Deciphering chemokine binding

Chemokines are small chemoattractant proteins that bind to chemokine receptors, which are members of the family of G protein–coupled receptors (GPCRs), to stimulate the directed migration of immune cells to sites of infection or inflammation. Monocyte chemoattractant proteins (MCPs) are chemokines that stimulate the receptor CCR2, which is found on monocytes and macrophages and is implicated in the pathogenesis of atherosclerosis and type 2 diabetes. Using chimeric MCP proteins and mutated CCR2 receptors, Huma et al. identified the N-terminal region of the chemokine as important for determining both receptor-binding affinity and the efficiency of receptor activation. The authors also showed that a region in the transmembrane domains of CCR2 was a critical site for chemokine-receptor interactions. These data may aid in the development of small-molecule inhibitors to treat diseases in which CCR2 signaling contributes to the pathology.

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