TY - JOUR

T1 - Specialisation of the venom gland proteome in predatory cone snails reveals functional diversification of the conotoxin biosynthetic pathway

AU - Safavi-Hemami, Helena

AU - Siero, William A

AU - Gorasia, Dhana G

AU - Young, Neil D

AU - Macmillan, David

AU - Williamson, Nicholas A

AU - Purcell, Anthony W

PY - 2011/9/2

Y1 - 2011/9/2

N2 - Conotoxins, venom peptides from marine cone snails, diversify rapidly as speciation occurs. It has been suggested that each species can synthesize between 1000 and 1900 different toxins with little to no interspecies overlap. Conotoxins exhibit an unprecedented degree of post-translational 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 161 and 157 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 catalyzing the formation and isomerization 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.

AB - Conotoxins, venom peptides from marine cone snails, diversify rapidly as speciation occurs. It has been suggested that each species can synthesize between 1000 and 1900 different toxins with little to no interspecies overlap. Conotoxins exhibit an unprecedented degree of post-translational 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 161 and 157 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 catalyzing the formation and isomerization 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.

KW - Amino Acid Sequence

KW - Animals

KW - Conotoxins/analysis

KW - Conus Snail/chemistry

KW - Electrophoresis, Gel, Two-Dimensional

KW - Histocytochemistry

KW - Molecular Sequence Data

KW - Protein Disulfide-Isomerases/chemistry

KW - Protein Folding

KW - Proteins/analysis

KW - Proteome/analysis

KW - Proteomics

KW - Species Specificity

U2 - 10.1021/pr1012976

DO - 10.1021/pr1012976

M3 - Journal article

C2 - 21707029

VL - 10

SP - 3904

EP - 3919

JO - Journal of Proteome Research

JF - Journal of Proteome Research

SN - 1535-3893

IS - 9

ER -