A Tale of Toxin Promiscuity: The Versatile Pharmacological Effects of Hcr 1b-2 Sea Anemone Peptide on Voltage-Gated Ion Channels.

Ernesto Lopes Pinheiro-Junior,Rimma Kalina,Elena Leychenko,Jan Tytgat,Irina Gladkikh,Steve Peigneur

doi:10.3390/md20020147

Abstract

Sea anemones are a rich source of biologically active compounds. Among approximately 1100 species described so far, Heteractis crispa species, also known as sebae anemone, is native to the Indo-Pacific area. As part of its venom components, the Hcr 1b-2 peptide was first described as an ASIC1a and ASIC3 inhibitor. Using Xenopus laevis oocytes and the two-electrode voltage-clamp technique, in the present work we describe the remarkable lack of selectivity of this toxin. Besides the acid-sensing ion channels previously described, we identified 26 new targets of this peptide, comprising 14 voltage-gated potassium channels, 9 voltage-gated sodium channels, and 3 voltage-gated calcium channels. Among them, Hcr 1b-2 is the first sea anemone peptide described to interact with isoforms from the Kv7 family and T-type Cav channels. Taken together, the diversity of Hcr 1b-2 targets turns this toxin into an interesting tool to study different types of ion channels, as well as a prototype to develop new and more specific ion channel ligands.

Highlights

Animal venoms are known as incredible libraries of active peptides, proteins, and neurotransmitters, among other components
Given the similarities between the Hcr 1b-2 and APETx1–4 peptides, we examined whether Hcr 1b-2 might have a promiscuous activity towards voltage-gated sodium channels
Two Cterminal residues were identified with a mass spectrometer MaXis impact (Bruker Daltonik, Karlsruhe, Germany) from the collision-induced dissociation tandem mass spectra of two peptide fragments obtained by the cyanogen bromide cleavage of the 4-vinylpyridinetreated Hcr 1b-2 [17]

Summary

A Tale of Toxin Promiscuity

Ernesto Lopes Pinheiro-Junior 1,* , Rimma Kalina 2, Irina Gladkikh 2, Elena Leychenko 2 , Jan Tytgat 1,* and Steve Peigneur 1,*. Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations

Introduction

Modulation of Nav Channels

Peptide Isolation and Primary Structure Determination

Findings

Conclusions