7VLA

Cryo-EM structure of the CCL15(27-92) bound CCR1-Gi complex

7VLA の概要

• エントリーDOI: 10.2210/pdb7vla/pdb
• EMDBエントリー: 32022
• 分子名称: Guanine nucleotide-binding protein G(i) subunit alpha-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, ... (7 entities in total)
• 機能のキーワード: gpcr, ccr1, chemokine receptor, membrne protein, membrane 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: 164152.53

構造登録者

Shao, Z.,Shen, Q.,Mao, C.,Yao, B.,Chen, L.,Zhang, H.,Shen, D.,Zhang, C.,Li, W.,Du, X.,Li, F.,Ma, H.,Chen, Z.,Xu, H.E.,Ying, S.,Zhang, Y.,Shen, H. (登録日: 2021-10-02, 公開日: 2022-03-23, 最終更新日: 2024-11-06)

主引用文献

Shao, Z.,Shen, Q.,Yao, B.,Mao, C.,Chen, L.N.,Zhang, H.,Shen, D.D.,Zhang, C.,Li, W.,Du, X.,Li, F.,Ma, H.,Chen, Z.H.,Xu, H.E.,Ying, S.,Zhang, Y.,Shen, H.
Identification and mechanism of G protein-biased ligands for chemokine receptor CCR1.
Nat.Chem.Biol., 18:264-271, 2022

PubMed Abstract: Biased signaling of G protein-coupled receptors describes an ability of different ligands that preferentially activate an alternative downstream signaling pathway. In this work, we identified and characterized different N-terminal truncations of endogenous chemokine CCL15 as balanced or biased agonists targeting CCR1, and presented three cryogenic-electron microscopy structures of the CCR1-G complex in the ligand-free form or bound to different CCL15 truncations with a resolution of 2.6-2.9 Å, illustrating the structural basis of natural biased signaling that initiates an inflammation response. Complemented with pharmacological and computational studies, these structures revealed it was the conformational change of Tyr291 (Y291) in CCR1 that triggered its polar network rearrangement in the orthosteric binding pocket and allosterically regulated the activation of β-arrestin signaling. Our structure of CCL15-bound CCR1 also exhibited a critical site for ligand binding distinct from many other chemokine-receptor complexes, providing new insights into the mode of chemokine recognition.

PubMed: 34949837
DOI: 10.1038/s41589-021-00918-z

実験手法

ELECTRON MICROSCOPY (2.7 Å)