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A 'conovenomic' analysis of the milked venom from the mollusk-hunting cone snail Conus textile-The pharmacological importance of post-translational modifications
Bergeron, Z.L.; Chun, J.B.; Baker, M.R.; Sandall, D.W.; Peigneur, S.; Yu, P.Y.C.; Thapa, P.; Milisen, J.W.; Tytgat, J.; Livett, B.G.; Bingham, J.P. (2013). A 'conovenomic' analysis of the milked venom from the mollusk-hunting cone snail Conus textile-The pharmacological importance of post-translational modifications. Peptides (New York, NY : 1980) 49: 145-158.
In: Peptides. Elsevier: New York etc.. ISSN 0196-9781; e-ISSN 1873-5169, more
Peer reviewed article  

Available in  Authors 
    VLIZ: Open Repository 279396 [ OMA ]

    Conus textile Linnaeus, 1758 [WoRMS]
Author keywords
    alpha-Conotoxin; Conopeptides; Conus textile; Mass spectrometry; Milkedvenom; Radula tooth; Post-translational modifications; nAChR

Authors  Top 
  • Bergeron, Z.L.
  • Chun, J.B.
  • Baker, M.R.
  • Sandall, D.W.
  • Peigneur, S., more
  • Yu, P.Y.C.
  • Thapa, P.
  • Milisen, J.W.
  • Tytgat, J., more
  • Livett, B.G.
  • Bingham, J.P.

    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 a-conotoxin TxIC. We assign this conopeptide to the 4/7 a-conotoxin family based on the peptide's sequence homology and cDNA pre-propeptide alignment. Pharmacologically, a-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]16a-conotoxin TxIC, demonstrates differential selectivity for the a3ß2 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 a-conotoxin TxIC from other a-conotoxins is the high degree of post-translational modification (44% of residues). This includes the incorporation of ?-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 a-conotoxins and illustrate a potential driver of toxin phyla-selectivity within Conus.

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