7XA3

Cryo-EM structure of the CCL2 bound CCR2-Gi complex

Summary for 7XA3

• Entry DOI: 10.2210/pdb7xa3/pdb
• EMDB information: 33086
• Descriptor: Isoform B of C-C chemokine receptor type 2, C-C motif chemokine 2, Guanine nucleotide-binding protein G(i) subunit alpha-1, ... (6 entities in total)
• Functional Keywords: gpcr, ccr2, chemokine receptor, membrne protein, membrane protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 6
• Total formula weight: 164291.46

Authors

Shao, Z.,Tan, Y.,Shen, Q.,Yao, B.,Hou, L.,Qin, J.,Xu, P.,Mao, C.,Chen, L.,Zhang, H.,Shen, D.,Zhang, C.,Li, W.,Du, X.,Li, F.,Chen, Z.,Jiang, Y.,Xu, H.E.,Ying, S.,Ma, H.,Zhang, Y.,Shen, H. (deposition date: 2022-03-17, release date: 2022-08-24, Last modification date: 2025-06-18)

Primary citation

Shao, Z.,Tan, Y.,Shen, Q.,Hou, L.,Yao, B.,Qin, J.,Xu, P.,Mao, C.,Chen, L.N.,Zhang, H.,Shen, D.D.,Zhang, C.,Li, W.,Du, X.,Li, F.,Chen, Z.H.,Jiang, Y.,Xu, H.E.,Ying, S.,Ma, H.,Zhang, Y.,Shen, H.
Molecular insights into ligand recognition and activation of chemokine receptors CCR2 and CCR3.
Cell Discov, 8:44-44, 2022

PubMed Abstract: Chemokine 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 Gα-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.

PubMed: 35570218
DOI: 10.1038/s41421-022-00403-4

Experimental method

ELECTRON MICROSCOPY (2.9 Å)