Crystal structure of human endothelin ET B receptor in complex with sarafotoxin S6b

Biochem Biophys Res Commun. 2020 Jul 23;528(2):383-388. doi: 10.1016/j.bbrc.2019.12.091. Epub 2020 Jan 28.

Abstract

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.

Keywords: Crystal structure; GPCR; Toxin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Crystallography, X-Ray
  • Humans
  • Models, Molecular
  • Receptor, Endothelin B / chemistry*
  • Viper Venoms / chemistry*

Substances

  • EDNRB protein, human
  • Receptor, Endothelin B
  • Viper Venoms
  • sarafotoxins s6