7xa3
Cryo-EM structure of the CCL2 bound CCR2-Gi complex
Structural highlights
FunctionCCR2_HUMAN Receptor for the CCL2, CCL7 and CCL13 chemokines. Transduces a signal by increasing intracellular calcium ion levels. Alternative coreceptor with CD4 for HIV-1 infection.[1] Publication Abstract from PubMedChemokine receptors are a family of G-protein-coupled receptors with key roles in leukocyte migration and inflammatory responses. Here, we present cryo-electron microscopy structures of two human CC chemokine receptor-G-protein complexes: CCR2 bound to its endogenous ligand CCL2, and CCR3 in the apo state. The structure of the CCL2-CCR2-G-protein complex reveals that CCL2 inserts deeply into the extracellular half of the transmembrane domain, and forms substantial interactions with the receptor through the most N-terminal glutamine. Extensive hydrophobic and polar interactions are present between both two chemokine receptors and the Galpha-protein, contributing to the constitutive activity of these receptors. Notably, complemented with functional experiments, the interactions around intracellular loop 2 of the receptors are found to be conserved and play a more critical role in G-protein activation than those around intracellular loop 3. Together, our findings provide structural insights into chemokine recognition and receptor activation, shedding lights on drug design targeting chemokine receptors. Molecular insights into ligand recognition and activation of chemokine receptors CCR2 and CCR3.,Shao Z, Tan Y, Shen Q, Hou L, Yao B, Qin J, Xu P, Mao C, Chen LN, Zhang H, Shen DD, Zhang C, Li W, Du X, Li F, Chen ZH, Jiang Y, Xu HE, Ying S, Ma H, Zhang Y, Shen H Cell Discov. 2022 May 15;8(1):44. doi: 10.1038/s41421-022-00403-4. PMID:35570218[2] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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