αD-Conotoxins in Species of the Eastern Pacific: The Case of from Mexico

Overview

Journal Toxins (Basel)

Publisher MDPI

Specialty Toxicology

Date 2019 Jul 25

PMID 31336928

Citations 3

Authors

Arisai C Hernandez-Samano

Andres Falcon

Fernando Zamudio

Cesar V F Batista

Jesus Emilio Michel-Morfin

Victor Landa-Jaime

Estuardo Lopez-Vera

Michael C Jeziorski

Manuel B Aguilar

Affiliations

Soon will be listed here.

Abstract

snails produce venoms containing numerous peptides such as the α-conotoxins (α-CTXs), which are well-known nicotinic acetylcholine receptor (nAChR) antagonists. Thirty-eight chromatographic fractions from venom extract were isolated by RP-HPLC. The biological activities of 37 fractions (0.07 µg/µL) were assayed by two-electrode voltage clamp on human α7 nAChRs expressed in oocytes. Fractions F7 and F16 notably inhibited the response elicited by acetylcholine by 52.7 ± 15.2% and 59.6 ± 2.5%, respectively. Fraction F7 was purified, and an active peptide (F7-3) was isolated. Using a combination of Edman degradation, mass spectrometry, and RNASeq, we determined the sequence of peptide F7-3: AVKKTCIRSTOGSNWGRCCLTKMCHTLCCARSDCTCVYRSGKGHGCSCTS, with one hydroxyproline (O) and a free C-terminus. The average mass of this peptide, 10,735.54 Da, indicates that it is a homodimer of identical subunits, with 10 disulfide bonds in total. This peptide is clearly similar to αD-CTXs from species of the Indo-Pacific. Therefore, we called it αD-PiXXA. This toxin slowly and reversibly inhibited the ACh-induced response of the hα7 nAChR subtype, with an IC of 6.2 μM, and it does not affect the hα3β2 subtype at 6.5 μM.

Citing Articles

A Novel Dimeric Conotoxin, FrXXA, from the Vermivorous Cone Snail , of the Eastern Pacific, Inhibits Nicotinic Acetylcholine Receptors.

Rodriguez-Ruiz X, Aguilar M, Ortiz-Arellano M, Safavi-Hemami H, Lopez-Vera E Toxins (Basel). 2022; 14(8).

PMID: 35893752 PMC: 9330476. DOI: 10.3390/toxins14080510.

Marine Origin Ligands of Nicotinic Receptors: Low Molecular Compounds, Peptides and Proteins for Fundamental Research and Practical Applications.

Kasheverov I, Kudryavtsev D, Shelukhina I, Nikolaev G, Utkin Y, Tsetlin V Biomolecules. 2022; 12(2).

PMID: 35204690 PMC: 8961598. DOI: 10.3390/biom12020189.

Conotoxin Diversity in the Venom Gland Transcriptome of the Magician's Cone, .

Pardos-Blas J, Irisarri I, Abalde S, Tenorio M, Zardoya R Mar Drugs. 2019; 17(10).

PMID: 31569823 PMC: 6835573. DOI: 10.3390/md17100553.

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