Citation

Safavi-Hemami H, Siero WA, Gorasia DG, Young ND, Macmillan D, Williamson NA, Purcell AW. J. Proteome Res. 2011; 10(9): 3904-3919.

Copyright

(Copyright © 2011, American Chemical Society)

DOI

10.1021/pr1012976

PMID

21707029

Abstract

Conotoxins, venom peptides from marine cone snails, diversify rapidly as speciation occurs. It has been suggested that each species can synthesise between 1000-1900 different toxins with little to no interspecies overlap. Conotoxins exhibit an unprecedented degree of posttranslational modifications, the most common one being the formation of disulfide bonds. Despite the great diversity of structurally complex peptides little is known about the glandular proteins responsible for their biosynthesis and maturation. Here, proteomic interrogations on the Conus venom gland led to the identification of novel glandular proteins of potential importance for toxin synthesis and secretion. A total of 131 and 123 proteins and protein isoforms were identified in the venom glands of Conus novaehollandiae and Conus victoriae respectively. Interspecies differences in the venom gland proteomes were apparent. A large proportion of the proteins identified function in protein/peptide translation, folding and protection events. Most intriguingly, however, we demonstrate the presence of a multitude of isoforms of protein disulfide isomerase (PDI), the enzyme catalysing the formation and isomerisation of the native disulfide bond. Investigating whether different PDI isoforms interact with distinct toxin families will greatly advance our knowledge on the generation of cone snail toxins and disulfide-rich peptides in general.

Language: en