Title: A 'conovenomic' analysis of the milked venom from the mollusk-hunting cone snail Conus textile--the pharmacological importance of post-translational modifications
Authors: Bergeron, Zachary L ×
Chun, Joycelyn B
Baker, Margaret R
Sandall, David W
Peigneur, Steve
Yu, Peter Y C
Thapa, Parashar
Milisen, Jeffrey W
Tytgat, Jan
Livett, Bruce G
Bingham, Jon-Paul #
Issue Date: Nov-2013
Publisher: Elsevier
Series Title: Peptides vol:49 pages:145-58
Article number: 10.1016/j.peptides.2013.09.004
Abstract: Cone snail venoms provide a largely untapped source of novel peptide drug leads. To enhance the discovery phase, a detailed comparative proteomic analysis was undertaken on milked venom from the mollusk-hunting cone snail, Conus textile, from three different geographic locations (Hawai'i, American Samoa and Australia's Great Barrier Reef). A novel milked venom conopeptide rich in post-translational modifications was discovered, characterized and named α-conotoxin TxIC. We assign this conopeptide to the 4/7 α-conotoxin family based on the peptide's sequence homology and cDNA pre-propeptide alignment. Pharmacologically, α-conotoxin TxIC demonstrates minimal activity on human acetylcholine receptor models (100 μM, <5% inhibition), compared to its high paralytic potency in invertebrates, PD50 = 34.2 nMol kg(-1). The non-post-translationally modified form, [Pro](2,8)[Glu](16)α-conotoxin TxIC, demonstrates differential selectivity for the α3β2 isoform of the nicotinic acetylcholine receptor with maximal inhibition of 96% and an observed IC50 of 5.4 ± 0.5 μM. Interestingly its comparative PD50 (3.6 μMol kg(-1)) in invertebrates was ~100 fold more than that of the native peptide. Differentiating α-conotoxin TxIC from other α-conotoxins is the high degree of post-translational modification (44% of residues). This includes the incorporation of γ-carboxyglutamic acid, two moieties of 4-trans hydroxyproline, two disulfide bond linkages, and C-terminal amidation. These findings expand upon the known chemical diversity of α-conotoxins and illustrate a potential driver of toxin phyla-selectivity within Conus.
ISSN: 0196-9781
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Toxicology and Pharmacology
× corresponding author
# (joint) last author

Files in This Item:

There are no files associated with this item.

Request a copy


All items in Lirias are protected by copyright, with all rights reserved.

© Web of science