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
Department of Biology, University of Utah, Salt Lake City, UT 84112; Department of Biology, University of Copenhagen, DK-2200 Copenhagen, Denmark;
Eccles institute of Human Genetics, University of Utah, Salt Lake City, UT 84112;
Proc Natl Acad Sci U S A. 2016 Mar 22;113(12):3227-32. doi: 10.1073/pnas.1525790113. Epub 2016 Mar 8.
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.
在内质网中形成正确的二硫键是折叠分泌型蛋白质的关键步骤。蛋白质二硫键异构酶（PDI）在此过程中发挥核心作用。我们报告了一个此前未被鉴定的、高度可变的PDI家族，它是迄今为止在单一属中描述的氧化还原酶中最多样化的基因家族。这些酶在捕食性芋螺的毒腺中特异性高表达，芋螺能合成种类极为多样的富含半胱氨酸的肽毒素（芋螺毒素）。这个PDI家族中的酶，称为芋螺毒素特异性PDI，能显著且有差异地加速几种芋螺毒素二硫键形成的动力学过程。我们的结果与一种与蛋白质折叠相关的独特生物学情况相符：一类折叠酶的多样化可能与超科芋螺科中有毒海蜗牛所表达的前所未有的富含二硫键结构域的快速进化相关。
