7CFN

Cryo-EM structure of the INT-777-bound GPBAR-Gs complex

7CFN の概要

• エントリーDOI: 10.2210/pdb7cfn/pdb
• EMDBエントリー: 30345
• 分子名称: Guanine nucleotide-binding protein G(s) subunit alpha isoforms short, 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, ... (9 entities in total)
• 機能のキーワード: gpcr, gpbar, complex, bile acid, membrane protein
• 由来する生物種: Homo sapiens (Human); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 142181.87

構造登録者

Yang, F.,Mao, C.,Guo, L.,Lin, J.,Ming, Q.,Xiao, P.,Wu, X.,Shen, Q.,Guo, S.,Shen, D.,Lu, R.,Zhang, L.,Huang, S.,Ping, Y.,Zhang, C.,Ma, C.,Zhang, K.,Liang, X.,Shen, Y.,Nan, F.,Yi, F.,Luca, V.,Zhou, J.,Jiang, C.,Sun, J.,Xie, X.,Yu, X.,Zhang, Y. (登録日: 2020-06-27, 公開日: 2020-09-09, 最終更新日: 2024-11-20)

主引用文献

Yang, F.,Mao, C.,Guo, L.,Lin, J.,Ming, Q.,Xiao, P.,Wu, X.,Shen, Q.,Guo, S.,Shen, D.D.,Lu, R.,Zhang, L.,Huang, S.,Ping, Y.,Zhang, C.,Ma, C.,Zhang, K.,Liang, X.,Shen, Y.,Nan, F.,Yi, F.,Luca, V.C.,Zhou, J.,Jiang, C.,Sun, J.P.,Xie, X.,Yu, X.,Zhang, Y.
Structural basis of GPBAR activation and bile acid recognition.
Nature, 587:499-504, 2020

PubMed Abstract: The G-protein-coupled bile acid receptor (GPBAR) conveys the cross-membrane signalling of a vast variety of bile acids and is a signalling hub in the liver-bile acid-microbiota-metabolism axis. Here we report the cryo-electron microscopy structures of GPBAR-G complexes stabilized by either the high-affinity P395 or the semisynthesized bile acid derivative INT-777 at 3 Å resolution. These structures revealed a large oval pocket that contains several polar groups positioned to accommodate the amphipathic cholic core of bile acids, a fingerprint of key residues to recognize diverse bile acids in the orthosteric site, a putative second bile acid-binding site with allosteric properties and structural features that contribute to bias properties. Moreover, GPBAR undertakes an atypical mode of activation and G protein coupling that features a different set of key residues connecting the ligand-binding pocket to the G-coupling site, and a specific interaction motif that is localized in intracellular loop 3. Overall, our study not only reveals unique structural features of GPBAR that are involved in bile acid recognition and allosteric effects, but also suggests the presence of distinct connecting mechanisms between the ligand-binding pocket and the G-protein-binding site in the G-protein-coupled receptor superfamily.

PubMed: 32698187
DOI: 10.1038/s41586-020-2569-1

実験手法

ELECTRON MICROSCOPY (3 Å)