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

18 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
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., ... 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, 113(12), 3227-3232. https://doi.org/10.1073/pnas.1525790113
Safavi-Hemami, Helena ; Li, Qing ; Jackson, Ronneshia L. ; Song, Albert S. ; Boomsma, Wouter ; Bandyopadhyay, Pradip K. ; Gruber, Christian W. ; Purcell, Anthony W. ; Yandell, Mark ; Olivera, Baldomero M. ; Ellgaard, Lars. / Rapid expansion of the protein disulfide isomerase gene family facilitates the folding of venom peptides. In: Proceedings of the National Academy of Sciences. 2016 ; Vol. 113, No. 12. pp. 3227-3232.
@article{29c37e72183449088541e5b695e06cb9,
title = "Rapid expansion of the protein disulfide isomerase gene family facilitates the folding of venom peptides",
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.",
keywords = "protein disulfide isomerase, peptide folding, gene expansion, cone snail venom, conotoxins",
author = "Helena Safavi-Hemami and Qing Li and Jackson, {Ronneshia L.} and Song, {Albert S.} and Wouter Boomsma and Bandyopadhyay, {Pradip K.} and Gruber, {Christian W.} and Purcell, {Anthony W.} and Mark Yandell and Olivera, {Baldomero M.} and Lars Ellgaard",
year = "2016",
month = "3",
day = "22",
doi = "10.1073/pnas.1525790113",
language = "English",
volume = "113",
pages = "3227--3232",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
publisher = "National Academy of Sciences",
number = "12",

}

Safavi-Hemami, H, Li, Q, Jackson, RL, Song, AS, Boomsma, W, Bandyopadhyay, PK, Gruber, CW, Purcell, AW, Yandell, M, Olivera, BM & 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, vol. 113, no. 12, pp. 3227-3232. https://doi.org/10.1073/pnas.1525790113

Rapid expansion of the protein disulfide isomerase gene family facilitates the folding of venom peptides. / Safavi-Hemami, Helena; Li, Qing; Jackson, Ronneshia L.; Song, Albert S.; Boomsma, Wouter; Bandyopadhyay, Pradip K.; Gruber, Christian W.; Purcell, Anthony W.; Yandell, Mark; Olivera, Baldomero M.; Ellgaard, Lars.

In: Proceedings of the National Academy of Sciences, Vol. 113, No. 12, 22.03.2016, p. 3227-3232.

Research output: Contribution to journalArticleResearchpeer-review

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

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.

KW - protein disulfide isomerase

KW - peptide folding

KW - gene expansion

KW - cone snail venom

KW - conotoxins

UR - http://www.ncbi.nlm.nih.gov/pubmed/26957604

U2 - 10.1073/pnas.1525790113

DO - 10.1073/pnas.1525790113

M3 - Article

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

SN - 0027-8424

IS - 12

ER -