%0 Journal Article
%T ¦ÁD-Conotoxins in Species of the Eastern Pacific: The Case of Conus princeps from Mexico
%A Andr¨¦s Falc¨®n
%A Arisa¨ª C. Hern¨¢ndez-S¨¢mano
%A C¨¦sar V.F. Batista
%A Estuardo L¨®pez-Vera
%A Fernando Zamudio
%A Jes¨²s Emilio Michel-Morf¨ªn
%A Manuel B. Aguilar
%A Michael C. Jeziorski
%A V¨ªctor Landa-Jaime
%J Archive of "Toxins".
%D 2019
%R 10.3390/toxins11070405
%X Conus snails produce venoms containing numerous peptides such as the ¦Á-conotoxins (¦Á-CTXs), which are well-known nicotinic acetylcholine receptor (nAChR) antagonists. Thirty-eight chromatographic fractions from Conus princeps venom extract were isolated by RP-HPLC. The biological activities of 37 fractions (0.07 ¦Ìg/¦ÌL) were assayed by two-electrode voltage clamp on human ¦Á7 nAChRs expressed in Xenopus laevis oocytes. Fractions F7 and F16 notably inhibited the response elicited by acetylcholine by 52.7 ¡À 15.2% and 59.6 ¡À 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 ¦ÁD-CTXs from species of the Indo-Pacific. Therefore, we called it ¦ÁD-PiXXA. This toxin slowly and reversibly inhibited the ACh-induced response of the h¦Á7 nAChR subtype, with an IC50 of 6.2 ¦ÌM, and it does not affect the h¦Á3¦Â2 subtype at 6.5 ¦ÌM
%K Cone snail
%K Conus princeps
%K ¦ÁD-conotoxin
%K nAChR
%K h¦Á7 nAChR
%K h¦Á3¦Â2 nAChR
%U https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6669827/