7VL8

Cryo-EM structure of the Apo CCR1-Gi complex

Summary for 7VL8

• Entry DOI: 10.2210/pdb7vl8/pdb
• EMDB information: 32020
• Descriptor: 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, ... (6 entities in total)
• Functional Keywords: gpcr, ccr1, chemokine receptor, membrne protein, membrane protein
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 5
• Total formula weight: 155934.02

Authors

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. (deposition date: 2021-10-02, release date: 2022-03-23, Last modification date: 2024-11-13)

Primary citation

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

Experimental method

ELECTRON MICROSCOPY (2.9 Å)