8SG1

Cryo-EM structure of CMKLR1 signaling complex

8SG1 の概要

• エントリーDOI: 10.2210/pdb8sg1/pdb
• EMDBエントリー: 40450
• 分子名称: 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)
• 機能のキーワード: gpcr, peptide agonist, chemerin9, membrane protein, signaling protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 146756.22

構造登録者

Zhang, X.,Zhang, C. (登録日: 2023-04-11, 公開日: 2023-11-01, 最終更新日: 2025-05-28)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (2.94 Å)