Crystal structures of human ET_B receptor provide mechanistic insight into receptor activation and partial activation.

ABSTRACT: Endothelin receptors (ET_A and ET_B) are class A GPCRs activated by vasoactive peptide endothelins, and are involved in blood pressure regulation. ET_B-selective signalling induces vasorelaxation, and thus selective ET_B agonists are expected to be utilized for improved anti-tumour drug delivery and neuroprotection. Here, we report the crystal structures of human ET_B receptor in complex with ET_B-selective agonist, endothelin-3 and an ET_B-selective endothelin analogue IRL1620. The structure of the endothelin-3-bound receptor reveals that the disruption of water-mediated interactions between W6.48 and D2.50 is critical for receptor activation, while these hydrogen-bonding interactions are partially preserved in the IRL1

SUBMITTER: Shihoya W 

PROVIDER: S-EPMC6226434 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature