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-Structure paper
タイトル | Structural basis of peptide recognition and activation of endothelin receptors. |
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ジャーナル・号・ページ | Nat Commun, Vol. 14, Issue 1, Page 1268, Year 2023 |
掲載日 | 2023年3月7日 |
著者 | Yujie Ji / Jia Duan / Qingning Yuan / Xinheng He / Gong Yang / Shengnan Zhu / Kai Wu / Wen Hu / Tianyu Gao / Xi Cheng / Hualiang Jiang / H Eric Xu / Yi Jiang / |
PubMed 要旨 | Endothelin system comprises three endogenous 21-amino-acid peptide ligands endothelin-1, -2, and -3 (ET-1/2/3), and two G protein-coupled receptor (GPCR) subtypes-endothelin receptor A (ETR) and B ...Endothelin system comprises three endogenous 21-amino-acid peptide ligands endothelin-1, -2, and -3 (ET-1/2/3), and two G protein-coupled receptor (GPCR) subtypes-endothelin receptor A (ETR) and B (ETR). Since ET-1, the first endothelin, was identified in 1988 as one of the most potent endothelial cell-derived vasoconstrictor peptides with long-lasting actions, the endothelin system has attracted extensive attention due to its critical role in vasoregulation and close relevance in cardiovascular-related diseases. Here we present three cryo-electron microscopy structures of ETR and ETR bound to ET-1 and ETR bound to the selective peptide IRL1620. These structures reveal a highly conserved recognition mode of ET-1 and characterize the ligand selectivity by ETRs. They also present several conformation features of the active ETRs, thus revealing a specific activation mechanism. Together, these findings deepen our understanding of endothelin system regulation and offer an opportunity to design selective drugs targeting specific ETR subtypes. |
リンク | Nat Commun / PubMed:36882417 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.99 - 3.5 Å |
構造データ | EMDB-34619, PDB-8hbd: EMDB-34663, PDB-8hcq: EMDB-34667, PDB-8hcx: |
由来 |
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キーワード | MEMBRANE PROTEIN (膜タンパク質) / IRL1620 / ETBR / Gi / ET1 / ETAR / Gq / scFv16 |