TY - JOUR
T1 - Rapid expansion of the protein disulfide isomerase gene family facilitates the folding of venom peptides
AU - Safavi-Hemami, Helena
AU - Li, Qing
AU - Jackson, Ronneshia L.
AU - Song, Albert S.
AU - Boomsma, Wouter Krogh
AU - Bandyopadhyay, Pradip K.
AU - Gruber, Christian W.
AU - Purcell, Anthony W.
AU - Yandell, Mark
AU - Olivera, Baldomero M.
AU - Ellgaard, Lars
PY - 2016/3/22
Y1 - 2016/3/22
N2 - Formation of correct disulfide bonds in the endoplasmic reticulum is a crucial step for folding proteins destined for secretion. Protein disulfide isomerases (PDIs) play a central role in this process. We report a previously unidentified, hypervariable family of 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, animals that synthesize a remarkably diverse set of cysteine-rich peptide toxins (conotoxins). Enzymes in this PDI family, termed conotoxin-specific PDIs, significantly and differentially accelerate the kinetics of disulfide-bond formation of several conotoxins. Our 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.
AB - Formation of correct disulfide bonds in the endoplasmic reticulum is a crucial step for folding proteins destined for secretion. Protein disulfide isomerases (PDIs) play a central role in this process. We report a previously unidentified, hypervariable family of 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, animals that synthesize a remarkably diverse set of cysteine-rich peptide toxins (conotoxins). Enzymes in this PDI family, termed conotoxin-specific PDIs, significantly and differentially accelerate the kinetics of disulfide-bond formation of several conotoxins. Our 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.
U2 - 10.1073/pnas.1525790113
DO - 10.1073/pnas.1525790113
M3 - Journal article
C2 - 26957604
SN - 0027-8424
VL - 113
SP - 3227
EP - 3232
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 12
ER -
