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-Structure paper
タイトル | Structural insight into apelin receptor-G protein stoichiometry. |
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ジャーナル・号・ページ | Nat Struct Mol Biol, Vol. 29, Issue 7, Page 688-697, Year 2022 |
掲載日 | 2022年7月11日 |
著者 | Yang Yue / Lier Liu / Li-Jie Wu / Yiran Wu / Ling Wang / Fei Li / Junlin Liu / Gye-Won Han / Bo Chen / Xi Lin / Rebecca L Brouillette / Émile Breault / Jean-Michel Longpré / Songting Shi / Hui Lei / Philippe Sarret / Raymond C Stevens / Michael A Hanson / Fei Xu / |
PubMed 要旨 | The technique of cryogenic-electron microscopy (cryo-EM) has revolutionized the field of membrane protein structure and function with a focus on the dominantly observed molecular species. This report ...The technique of cryogenic-electron microscopy (cryo-EM) has revolutionized the field of membrane protein structure and function with a focus on the dominantly observed molecular species. This report describes the structural characterization of a fully active human apelin receptor (APJR) complexed with heterotrimeric G protein observed in both 2:1 and 1:1 stoichiometric ratios. We use cryo-EM single-particle analysis to determine the structural details of both species from the same sample preparation. Protein preparations, in the presence of the endogenous peptide ligand ELA or a synthetic small molecule, both demonstrate these mixed stoichiometric states. Structural differences in G protein engagement between dimeric and monomeric APJR suggest a role for the stoichiometry of G protein-coupled receptor- (GPCR-)G protein coupling on downstream signaling and receptor pharmacology. Furthermore, a small, hydrophobic dimer interface provides a starting framework for additional class A GPCR dimerization studies. Together, these findings uncover a mechanism of versatile regulation through oligomerization by which GPCRs can modulate their signaling. |
リンク | Nat Struct Mol Biol / PubMed:35817871 |
手法 | EM (単粒子) / X線回折 |
解像度 | 2.7 - 4.21 Å |
構造データ | EMDB-32243, PDB-7w0l: EMDB-32244, PDB-7w0m: EMDB-32245, PDB-7w0n: EMDB-32246, PDB-7w0o: EMDB-32247, PDB-7w0p: PDB-7sus: |
化合物 | ChemComp-ZN: ChemComp-8EH: ChemComp-OLC: ChemComp-HOH: |
由来 |
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キーワード | MEMBRANE PROTEIN / GPCR / Class A GPCR / small molecule / Apelin receptor / Complex / Dimerization |