7ZLY

Crystal structure of human GPCR Niacin receptor (HCA2) expressed from Spodoptera frugiperda

7ZLY の概要

• エントリーDOI: 10.2210/pdb7zly/pdb
• 分子名称: Hydroxycarboxylic acid receptor 2,Soluble cytochrome b562, OLEIC ACID, (2R)-2,3-dihydroxypropyl (9Z)-octadec-9-enoate (3 entities in total)
• 機能のキーワード: niacin receptor, hydroxycarboxylic acid receptor 2, hca2, gpcr, membrane protein structure, membrane protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 51868.83

構造登録者

Yang, Y.,Kang, H.J.,Gao, R.G.,Wang, J.J.,FiBerto, J.F.,Wu, L.J.,Tong, J.H.,Han, G.W.,Qu, L.,Wu, Y.R.,Pileski, R.,Li, X.M.,Zhang, X.C.,Zhao, S.W.,Kenakin, T.,Wang, Q.,Stevens, R.C.,Peng, W.,Roth, B.L.,Rao, Z.H.,Liu, Z.J. (登録日: 2022-04-17, 公開日: 2023-04-12, 最終更新日: 2024-10-16)

主引用文献

Yang, Y.,Kang, H.J.,Gao, R.,Wang, J.,Han, G.W.,DiBerto, J.F.,Wu, L.,Tong, J.,Qu, L.,Wu, Y.,Pileski, R.,Li, X.,Zhang, X.C.,Zhao, S.,Kenakin, T.,Wang, Q.,Stevens, R.C.,Peng, W.,Roth, B.L.,Rao, Z.,Liu, Z.J.
Structural insights into the human niacin receptor HCA2-G i signalling complex.
Nat Commun, 14:1692-1692, 2023

PubMed Abstract: The hydroxycarboxylic acid receptor 2 (HCA2) agonist niacin has been used as treatment for dyslipidemia for several decades albeit with skin flushing as a common side-effect in treated individuals. Extensive efforts have been made to identify HCA2 targeting lipid lowering agents with fewer adverse effects, despite little being known about the molecular basis of HCA2 mediated signalling. Here, we report the cryo-electron microscopy structure of the HCA2-G signalling complex with the potent agonist MK-6892, along with crystal structures of HCA2 in inactive state. These structures, together with comprehensive pharmacological analysis, reveal the ligand binding mode and activation and signalling mechanisms of HCA2. This study elucidates the structural determinants essential for HCA2 mediated signalling and provides insights into ligand discovery for HCA2 and related receptors.

PubMed: 36973264
DOI: 10.1038/s41467-023-37177-6

実験手法

X-RAY DIFFRACTION (2.7 Å)