8SG1

Cryo-EM structure of CMKLR1 signaling complex

Summary for 8SG1

• Entry DOI: 10.2210/pdb8sg1/pdb
• EMDB information: 40450
• Descriptor: Chemerin-like receptor 1, Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, Guanine nucleotide-binding protein G(I)/G(S)/G(O) subunit gamma-2, ... (8 entities in total)
• Functional Keywords: gpcr, peptide agonist, chemerin9, membrane protein, signaling protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 6
• Total formula weight: 146756.22

Authors

Zhang, X.,Zhang, C. (deposition date: 2023-04-11, release date: 2023-11-01, Last modification date: 2025-05-28)

Primary citation

Zhang, X.,Weiss, T.,Cheng, M.H.,Chen, S.,Ambrosius, C.K.,Czerniak, A.S.,Li, K.,Feng, M.,Bahar, I.,Beck-Sickinger, A.G.,Zhang, C.
Structural basis of G protein-Coupled receptor CMKLR1 activation and signaling induced by a chemerin-derived agonist.
Plos Biol., 21:e3002188-e3002188, 2023

PubMed Abstract: Chemokine-like receptor 1 (CMKLR1), also known as chemerin receptor 23 (ChemR23) or chemerin receptor 1, is a chemoattractant G protein-coupled receptor (GPCR) that responds to the adipokine chemerin and is highly expressed in innate immune cells, including macrophages and neutrophils. The signaling pathways of CMKLR1 can lead to both pro- and anti-inflammatory effects depending on the ligands and physiological contexts. To understand the molecular mechanisms of CMKLR1 signaling, we determined a high-resolution cryo-electron microscopy (cryo-EM) structure of the CMKLR1-Gi signaling complex with chemerin9, a nanopeptide agonist derived from chemerin, which induced complex phenotypic changes of macrophages in our assays. The cryo-EM structure, together with molecular dynamics simulations and mutagenesis studies, revealed the molecular basis of CMKLR1 signaling by elucidating the interactions at the ligand-binding pocket and the agonist-induced conformational changes. Our results are expected to facilitate the development of small molecule CMKLR1 agonists that mimic the action of chemerin9 to promote the resolution of inflammation.

PubMed: 38055679
DOI: 10.1371/journal.pbio.3002188

Experimental method

ELECTRON MICROSCOPY (2.94 Å)