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TitleStructural basis of peptide recognition and activation of endothelin receptors.
Journal, issue, pagesNat Commun, Vol. 14, Issue 1, Page 1268, Year 2023
Publish dateMar 7, 2023
AuthorsYujie 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 AbstractEndothelin 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.
External linksNat Commun / PubMed:36882417 / PubMed Central
MethodsEM (single particle)
Resolution2.99 - 3.5 Å
Structure data

34619

8hbd

EMDB-34619, PDB-8hbd:
Cryo-EM structure of IRL1620-bound ETBR-Gi complex
Method: EM (single particle) / Resolution: 2.99 Å

34663

8hcq

EMDB-34663, PDB-8hcq:
Cryo-EM structure of endothelin1-bound ETAR-Gq complex
Method: EM (single particle) / Resolution: 3.01 Å

34667

8hcx

EMDB-34667, PDB-8hcx:
Cryo-EM structure of Endothelin1-bound ETBR-Gq complex
Method: EM (single particle) / Resolution: 3.5 Å

Source
  • homo sapiens (human)
  • mus musculus (house mouse)
  • Homo (humans)
KeywordsMEMBRANE PROTEIN / IRL1620 / ETBR / Gi / ET1 / ETAR / Gq / scFv16

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