Rapid expansion of the protein disulfide isomerase gene family facilitates the folding of venom peptides

Helena Safavi-Hemami, Qing Li, Ronneshia L. Jackson, Albert S. Song, Wouter Krogh Boomsma, Pradip K. Bandyopadhyay, Christian W. Gruber, Anthony W. Purcell, Mark Yandell, Baldomero M. Olivera, Lars Ellgaard

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44 Citationer (Scopus)

Abstract

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.

OriginalsprogEngelsk
TidsskriftProceedings of the National Academy of Sciences of the United States of America
Vol/bind113
Udgave nummer12
Sider (fra-til)3227-3232
Antal sider6
ISSN0027-8424
DOI
StatusUdgivet - 2016

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