5glh | pdb_00005glh
Human endothelin receptor type-B in complex with ET-1
Structural highlights
DiseaseEDNRB_HUMAN Hirschsprung disease;Waardenburg-Shah syndrome. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. Defects in EDNRB are associated with Waardenburg syndrome 2, with ocular albinism, autosomal recessive: A disorder characterized by the association of features typical of Waardenburg syndrome type 2 with ocular albinism. Patients manifest reduced visual acuity, albinotic fundus, deafness, hypomelanosis.[1] FunctionENLYS_BPT4 Endolysin with lysozyme activity that degrades host peptidoglycans and participates with the holin and spanin proteins in the sequential events which lead to the programmed host cell lysis releasing the mature viral particles. Once the holin has permeabilized the host cell membrane, the endolysin can reach the periplasm and break down the peptidoglycan layer.[2] EDNRB_HUMAN Non-specific receptor for endothelin 1, 2, and 3. Mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system.[3] Publication Abstract from PubMedEndothelin, 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. Activation mechanism of endothelin ETB receptor by endothelin-1.,Shihoya W, Nishizawa T, Okuta A, Tani K, Dohmae N, Fujiyoshi Y, Nureki O, Doi T Nature. 2016 Sep 5;537(7620):363-368. doi: 10.1038/nature19319. PMID:27595334[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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