8HBD

Cryo-EM structure of IRL1620-bound ETBR-Gi complex

Summary for 8HBD

• Entry DOI: 10.2210/pdb8hbd/pdb
• EMDB information: 34619
• Descriptor: 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)
• Functional Keywords: irl1620, etbr, gi, membrane protein
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 6
• Total formula weight: 189444.40

Authors

Yuan, Q.,Ji, Y.,Jiang, Y.,Duan, J.,Xu, H.E. (deposition date: 2022-10-28, release date: 2023-03-22, Last modification date: 2023-10-04)

Primary citation

Ji, Y.,Duan, J.,Yuan, Q.,He, X.,Yang, G.,Zhu, S.,Wu, K.,Hu, W.,Gao, T.,Cheng, X.,Jiang, H.,Eric Xu, H.,Jiang, Y.
Structural basis of peptide recognition and activation of endothelin receptors.
Nat Commun, 14:1268-1268, 2023

PubMed Abstract: 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.

PubMed: 36882417
DOI: 10.1038/s41467-023-36998-9

Experimental method

ELECTRON MICROSCOPY (2.99 Å)