Crystal structure of human endothelin ETB receptor in complex with sarafotoxin S6b.

Tamaki Izume, Hirotake Miyauchi, Wataru Shihoya, Osamu Nureki

Biochemical and biophysical research communications 2020 Jul 23

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Sarafotoxins (SRTXs) are endothelin-like peptides extracted from snake venom. SRTXs stimulate the endothelin ETA and ETB receptors and enhance vasoconstriction, followed by left ventricular dysfunction and bronchoconstriction. SRTXs include four major isopeptides, S6a-d, with different subtype selectivities. Here, we report the crystal structure of the human ETB receptor in complex with the non-selective sarafotoxin S6b at 3.0 Å resolution. This structure reveals the similarities and differences between the binding modes of the endothelins and S6b. Moreover, molecular dynamics simulations based on the S6b-bound receptor provides structural insight into the subtype selectivity of the sarafotoxins. Our study clarifies the recognition mechanism of the endothelin-like peptide families. Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Tamaki Izume, Hirotake Miyauchi, Wataru Shihoya, Osamu Nureki. Crystal structure of human endothelin ETB receptor in complex with sarafotoxin S6b. Biochemical and biophysical research communications. 2020 Jul 23;528(2):383-388