Structure of the O-Glycosylated Conopeptide CcTx from Conus consors Venom

Abstract

The glycopeptide CcTx, isolated from the venom of the piscivorous cone snail Conus consors, belongs to the kA-family of conopeptides. These toxins elicit excitotoxic re- ACHTUNGTRENUNGsponses in the prey by acting on voltage- gated sodium channels. The structure of CcTx, a first in the kA-family, has been determined by high-resolution NMR spectroscopy together with the analysis of its O-glycan at Ser7. A new type of glycopeptide O-glycan core structure, here registered as core type 9, containing two terminal l-galactose units {a-l-Galp-(1!4)-a-d- GlcpNAc-(1!6)-[a-l-Galp-(1!2)-b-d- Galp-(1!3)-]a-d-GalpNAc-(1!O)}, is highlighted. A sequence comparison to other putative members of the kAfamily suggests that O-linked glycosylation might be more common than previously thought. This observation alone underlines the requirement for more careful and in-depth investigations into this type of post-translational modification in conotoxins.