8WSS

Cryo-EM structure of Melanin-Concentrating Hormone Receptor 1 with MCH

8WSS の概要

• エントリーDOI: 10.2210/pdb8wss/pdb
• EMDBエントリー: 37823
• 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, ... (6 entities in total)
• 機能のキーワード: melanin-concentrating hormone receptors1, gpcr, 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: 165802.74

構造登録者

Zhao, L.,He, Q.,Yuan, Q.,Gu, Y.,Shan, H.,Hu, W.,Wu, K.,Xu, H.E.,Zhang, Y.,Wu, C. (登録日: 2023-10-17, 公開日: 2024-06-19, 最終更新日: 2024-10-16)

主引用文献

He, Q.,Yuan, Q.,Shan, H.,Wu, C.,Gu, Y.,Wu, K.,Hu, W.,Zhang, Y.,He, X.,Xu, H.E.,Zhao, L.H.
Mechanisms of ligand recognition and activation of melanin-concentrating hormone receptors.
Cell Discov, 10:48-48, 2024

PubMed Abstract: Melanin-concentrating hormone (MCH) is a cyclic neuropeptide that regulates food intake, energy balance, and other physiological functions by stimulating MCHR1 and MCHR2 receptors, both of which are class A G protein-coupled receptors. MCHR1 predominately couples to inhibitory G protein, G, and MCHR2 can only couple to G. Here we present cryo-electron microscopy structures of MCH-activated MCHR1 with G and MCH-activated MCHR2 with G at the global resolutions of 3.01 Å and 2.40 Å, respectively. These structures reveal that MCH adopts a consistent cysteine-mediated hairpin loop configuration when bound to both receptors. A central arginine from the LGRVY core motif between the two cysteines of MCH penetrates deeply into the transmembrane pocket, triggering receptor activation. Integrated with mutational and functional insights, our findings elucidate the molecular underpinnings of ligand recognition and MCH receptor activation and offer a structural foundation for targeted drug design.

PubMed: 38710677
DOI: 10.1038/s41421-024-00679-8

実験手法

ELECTRON MICROSCOPY (3.01 Å)