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 Boomsma, Pradip K. Bandyopadhyay, Christian W. Gruber, Anthony W. Purcell, Mark Yandell, Baldomero M. Olivera, Lars Ellgaard

Research output: Contribution to journalArticleResearchpeer-review

22 Citations (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.
Original languageEnglish
Pages (from-to)3227-3232
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number12
DOIs
Publication statusPublished - 22 Mar 2016

Keywords

  • protein disulfide isomerase
  • peptide folding
  • gene expansion
  • cone snail venom
  • conotoxins

Cite this

Safavi-Hemami, H., Li, Q., Jackson, R. L., Song, A. S., Boomsma, W., Bandyopadhyay, P. K., Gruber, C. W., Purcell, A. W., Yandell, M., Olivera, B. M., & Ellgaard, L. (2016). Rapid expansion of the protein disulfide isomerase gene family facilitates the folding of venom peptides. Proceedings of the National Academy of Sciences of the United States of America, 113(12), 3227-3232. https://doi.org/10.1073/pnas.1525790113