5GLH

Human endothelin receptor type-B in complex with ET-1

Summary for 5GLH

• Entry DOI: 10.2210/pdb5glh/pdb
• Related: 5GLI
• Descriptor: Endothelin Receptor Subtype-B, Peptide from Endothelin-1 (3 entities in total)
• Functional Keywords: alpha helical, signaling protein
• Biological source: Homo sapiens; More
• Total number of polymer chains: 2
• Total formula weight: 58454.68

Authors

Shihoya, W.,Nishizawa, T.,Okuta, A.,Tani, K.,Fujiyoshi, Y.,Dohmae, N.,Nureki, O.,Doi, T. (deposition date: 2016-07-11, release date: 2016-09-07, Last modification date: 2024-11-20)

Primary citation

Shihoya, W.,Nishizawa, T.,Okuta, A.,Tani, K.,Dohmae, N.,Fujiyoshi, Y.,Nureki, O.,Doi, T.
Activation mechanism of endothelin ETB receptor by endothelin-1.
Nature, 537:363-368, 2016

PubMed Abstract: Endothelin, a 21-amino-acid peptide, participates in various physiological processes, such as regulation of vascular tone, humoral homeostasis, neural crest cell development and neurotransmission. Endothelin and its G-protein-coupled receptor are involved in the development of various diseases, such as pulmonary arterial hypertension, and thus are important therapeutic targets. Here we report crystal structures of human endothelin type B receptor in the ligand-free form and in complex with the endogenous agonist endothelin-1. The structures and mutation analysis reveal the mechanism for the isopeptide selectivity between endothelin-1 and -3. Transmembrane helices 1, 2, 6 and 7 move and envelop the entire endothelin peptide, in a virtually irreversible manner. The agonist-induced conformational changes are propagated to the receptor core and the cytoplasmic G-protein coupling interface, and probably induce conformational flexibility in TM6. A comparison with the M2 muscarinic receptor suggests a shared mechanism for signal transduction in class A G-protein-coupled receptors.

PubMed: 27595334
DOI: 10.1038/nature19319

Experimental method

X-RAY DIFFRACTION (2.8 Å)