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-Structure paper
タイトル | Cryo-EM structure of the human somatostatin receptor 2 complex with its agonist somatostatin delineates the ligand-binding specificity. |
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ジャーナル・号・ページ | Elife, Vol. 11, Year 2022 |
掲載日 | 2022年4月21日 |
著者 | Yunseok Heo / Eojin Yoon / Ye-Eun Jeon / Ji-Hye Yun / Naito Ishimoto / Hyeonuk Woo / Sam-Yong Park / Ji-Joon Song / Weontae Lee / |
PubMed 要旨 | 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 ...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. |
リンク | Elife / PubMed:35446253 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.72 Å |
構造データ | EMDB-32543, PDB-7wj5: |
由来 |
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キーワード | MEMBRANE PROTEIN/IMMUNE SYSTEM / GPCR / agonist / heterotrimeric G-protein / cAMP / MEMBRANE PROTEIN / MEMBRANE PROTEIN-IMMUNE SYSTEM complex |