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.
authors.affiliation: Department of Biology, University of Utah, Salt Lake City, UT 84112; Department of Biology, University of Copenhagen, DK-2200 Copenhagen, Denmark; helena.safavi@utah.edu olivera@biology.utah.edu.
authors.forename: Helena
authors.initials: H
authors.lastname: Safavi-Hemami
authors.affiliation: Eccles institute of Human Genetics, University of Utah, Salt Lake City, UT 84112;
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.affiliation: Department of Biology, University of Utah, Salt Lake City, UT 84112;
authors.forename: Ronneshia L
authors.initials: RL
authors.lastname: Jackson
authors.affiliation: Department of Biology, University of Utah, Salt Lake City, UT 84112;
authors.forename: Albert S
authors.initials: AS
authors.lastname: Song
authors.affiliation: Department of Biology, University of Copenhagen, DK-2200 Copenhagen, Denmark;
authors.forename: Wouter
authors.initials: W
authors.lastname: Boomsma
authors.affiliation: Department of Biology, University of Utah, Salt Lake City, UT 84112;
authors.forename: Pradip K
authors.initials: PK
authors.lastname: Bandyopadhyay
authors.affiliation: Center for Physiology and Pharmacology, Medical University of Vienna, A-1090, Vienna, Austria; School of Biomedical Sciences, University of Queensland, St. Lucia, Queensland 4072, Australia;
authors.forename: Christian W
authors.initials: CW
authors.lastname: Gruber
authors.affiliation: Infection and Immunity Program, Monash Biomedicine Discovery Institute, Monash University, Clayton, Victoria 3800, Australia; Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia;
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Purcell
authors.affiliation: Eccles institute of Human Genetics, University of Utah, Salt Lake City, UT 84112; Utah Science Technology and Research Center for Genetic Discovery, University of Utah, Salt Lake City, UT 84112.
authors.forename: Mark
authors.initials: M
authors.lastname: Yandell
authors.affiliation: Department of Biology, University of Utah, Salt Lake City, UT 84112; helena.safavi@utah.edu olivera@biology.utah.edu.
authors.forename: Baldomero M
authors.initials: BM
authors.lastname: Olivera
authors.affiliation: Department of Biology, University of Copenhagen, DK-2200 Copenhagen, Denmark;
authors.forename: Lars
authors.identifier: http://orcid.org/0000-0002-7018-0137
authors.initials: L
authors.lastname: Ellgaard
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D052078:Conus Snail; D008969:Molecular Sequence Data; D008978:Mollusk Venoms / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D019704:Protein Disulfide-Isomerases / Q000737:chemistry / Q000235:genetics*; D017510:Protein Folding; D017386:Sequence Homology, Amino Acid
chemical_list: D008978:Mollusk Venoms; D010455:Peptides; D019704:Protein Disulfide-Isomerases
keywords: cone snail venom; conotoxins; gene expansion; peptide folding; protein disulfide isomerase