Institute:University of Copenhagen
Title:Expansion and diversification of the PDI gene facilitates oxidative folding of disulfide-rich cone snail toxins
Location:RUPPERT 116
Abstract:["Predatory marine cone snails of the genus Conus synthesize a great diversity of disulfide-rich neuropeptides referred to as conotoxins.\r\nConotoxins selectively target specific subtypes of receptors or ion channels throughout the nervous system, a characteristic that has lead to wide use of conotoxins in ion channel research and as therapeutic agents.\r\n\r\nHere, I will present our recent identification of a hypervariable family of Protein Disulfide Isomerases (PDIs) that represents the most diverse gene family of oxidoreductases described in a single genus to date. These enzymes are highly expressed specifically in the venom glands of predatory cone snails. Enzymes in this PDI family, termed conotoxin-specific PDIs (csPDIs), significantly and differentially accelerate the kinetics of disulfide-bond formation of several conotoxins. The results are consistent with a unique biological scenario associated with protein folding: The diversification of a family of foldases can be correlated with the rapid evolution of an unprecedented diversity of disulfide-rich structural domains expressed by venomous marine snails in the superfamily Conoidea.\r\n\r\nIn addition, I will present ongoing efforts to establish an E. coli expression system that will allow the production and molecular characterization of a variety of conotoxins and other disulfide-rich peptides of biomedical or research interest."]
Host:Ineke Braakman