7WJ5

Cryo-EM structure of human somatostatin receptor 2 complex with its agonist somatostatin delineates the ligand binding specificity

7WJ5 の概要

• エントリーDOI: 10.2210/pdb7wj5/pdb
• EMDBエントリー: 32543
• 関連するBIRD辞書のPRD_ID: PRD_001216
• 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: gpcr, agonist, heterotrimeric g-protein, camp, membrane protein, membrane protein-immune system complex, membrane protein/immune system
• 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: 176136.43

構造登録者

Heo, Y.S.,Yoon, E.J.,Jeon, Y.E.,Yun, J.-H.,Ishimoto, N.,Woo, H.,Park, S.Y.,Song, J.,Lee, W.T. (登録日: 2022-01-05, 公開日: 2022-07-13, 最終更新日: 2024-11-06)

主引用文献

Heo, Y.,Yoon, E.,Jeon, Y.E.,Yun, J.H.,Ishimoto, N.,Woo, H.,Park, S.Y.,Song, J.J.,Lee, W.
Cryo-EM structure of the human somatostatin receptor 2 complex with its agonist somatostatin delineates the ligand-binding specificity.
Elife, 11:-, 2022

PubMed Abstract: Somatostatin is a peptide hormone that regulates endocrine systems by binding to G-protein-coupled somatostatin receptors. Somatostatin receptor 2 (SSTR2) is a human somatostatin receptor and is highly implicated in hormone disorders, cancers, and neurological diseases. Here, we report the high-resolution cryo-EM structure of full-length human SSTR2 bound to the agonist somatostatin (SST-14) in complex with inhibitory G (G) proteins. Our structural and mutagenesis analyses show that seven transmembrane helices form a deep pocket for ligand binding and that SSTR2 recognizes the highly conserved Trp-Lys motif of SST-14 at the bottom of the pocket. Furthermore, our sequence analysis combined with AlphaFold modeled structures of other SSTR isoforms provide a structural basis for the mechanism by which SSTR family proteins specifically interact with their cognate ligands. This work provides the first glimpse into the molecular recognition mechanism of somatostatin receptors and a crucial resource to develop therapeutics targeting somatostatin receptors.

PubMed: 35446253
DOI: 10.7554/eLife.76823

実験手法

ELECTRON MICROSCOPY (3.72 Å)