Chemokine receptors are a family of G-protein-coupled receptors that regulate the migration of immune cells; their function has been implicated in a range of diseases. Two groups reporting in this issue of Nature describe crystal structures of two different chemokine receptors bound to small-molecule inhibitors. Tracy Handel and colleagues describe the structure of CCR2—a promising drug target for autoimmune, inflammatory and metabolic diseases as well as cancer—bound to orthosteric (BMS-681) and allosteric (CCR2-RA-[R]) antagonists. Fiona Marshall and colleagues describe the structure of CCR9—involved in immune cell recruitment to the gut and a promising drug target in inflammatory bowel disease—in complex with the selective CCR9 antagonist vercirnon. Both CCR2 and CCR9 structures reveal an allosteric pocket on the cytoplasmic face of the receptor. This allosteric pocket appears to be highly druggable, and homologous pockets may be present on other chemokine receptors.
- Inside-out receptor inhibition (News & Views p344, doi: 10.1038/nature20486)
- Structure of CC chemokine receptor 2 with orthosteric and allosteric antagonists (Letter p458, doi: 10.1038/nature20605)
- Intracellular allosteric antagonism of the CCR9 receptor (Letter p462, doi: 10.1038/nature20606)
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