A turripeptide from Polystira nobilis venom inhibits human α3β2 and α7 nicotinic acetylcholine receptors. (September 2020)

• Record Type: Journal Article
• Authors: Hernández-Sámano, Arisaí C.; Falcón, Andrés; Zamudio, Fernando; Ortíz- Arellano, Mónica A.; López-Vera, Estuardo; Aguilar, Manuel B.
• Is Part Of: Insect biochemistry and molecular biology. Volume 124(2020)
• Publication Date: 2020-09
• Subjects: Turrid snail -- Polystira nobilis -- Turritoxin -- Nicotinic acetylcholine receptor -- α3β2 receptor -- α7 receptor; Insect biochemistry -- Periodicals; Insects -- Physiology -- Periodicals; Insects -- Molecular aspects -- Periodicals; Biochemistry -- Periodicals; Insectes -- Biochimie -- Périodiques; Insectes -- Composition -- Périodiques; Insectes -- Physiologie -- Périodiques; Insectes -- Aspect moléculaire -- Périodiques; Biochimie -- Périodiques; Biochemistry; Insect biochemistry; Insects -- Molecular aspects; Insects -- Physiology; Periodicals; 572.8157
• DOI: 10.1016/j.ibmb.2020.103416
• Languages: English
• ISSNs: 0965-1748

Abstract

Abstract: Almost all marine snails within superfamily Conoidea produce venoms containing numerous neuroactive peptides. Most toxins characterized from members of this superfamily are produced by species belonging to family Conidae. These toxins (conotoxins) affect diverse membrane proteins, such as voltage- and ligand-gated ion channels, including nicotinic acetylcholine receptors (nAChRs). Family Turridae has been considerably less studied than their Conidae counterpart and, therefore, turrid toxins (turritoxins) have just been barely described. Consequently, in this work the most prominent chromatographic (RP-HPLC) fractions from the East Pacific species Polystira nobilis venom duct extract were isolated. The biological activity of six selected fractions was assayed on human (h) α7 AChRs expressed in Xenopus laevis oocytes. One of these fractions, F21, inhibited the acetylcholine-elicited response by 62 ± 12%. Therefore, this fraction was further purified and the F21-2 peptide was obtained. This peptide (at 5.6 μM) strongly and irreversibly inhibited the acetylcholine-induced response on hα7 and hα3β2 nAChRs, by 55 ± 4 and 91 ± 1%, respectively. Electrospray mass spectrometry indicates that the average molecular mass of this toxin is 12 358.80 Da. The affinity for hα3β2 nAChRs is high (IC50 of 566.2 nM). A partial sequence without cysteines was obtained by automated Edman degradation: WFRSFKSYYGHHGSVYRPNEPNFRSFAS…; blastp search revealed that this sequence has low similarity to some non-Cys-containing turripeptides. This is the first report of a turritoxin from a species of the American Pacific and the second description of a turripeptide inhibiting nAChRs. Graphical abstract: Image 1 Highlights: A turripeptide from a species of the Eastern Pacific was purified for the first time. Peptide F21-2 was characterized from Polystira nobilis . F21-2 is the first nAChR-inhibiting toxin from the genus Polystira . Peptide F21-2 strongly and irreversibly inhibits human α3β2 and α7 nAChRs. Peptide F21-2 is the second turripeptide shown to inhibit nAChRs.