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Publication Abstract from PubMed

Disulfide-rich peptides (DRPs) play diverse physiological roles and have emerged as attractive sources of pharmacological tools and drug leads. Here we describe the 3D structure of a centipede venom peptide, U-SLPTX15-Sm2a, whose family defines a unique class of one of the most widespread DRP folds known, the cystine-stabilized alpha/beta fold (CSalphabeta). This class, which we have named the two-disulfide CSalphabeta fold (2ds-CSalphabeta), contains only two internal disulfide bonds as opposed to at least three in all other confirmed CSalphabeta peptides, and constitutes one of the major neurotoxic peptide families in centipede venoms. We show the 2ds-CSalphabeta is widely distributed outside centipedes and is likely an ancient fold predating the split between prokaryotes and eukaryotes. Our results provide insights into the ancient evolutionary history of a widespread DRP fold and highlight the usefulness of 3D structures as evolutionary tools.

A Centipede Toxin Family Defines an Ancient Class of CSalphabeta Defensins.,Dash TS, Shafee T, Harvey PJ, Zhang C, Peigneur S, Deuis JR, Vetter I, Tytgat J, Anderson MA, Craik DJ, Durek T, Undheim EAB Structure. 2019 Feb 5;27(2):315-326.e7. doi: 10.1016/j.str.2018.10.022. Epub 2018, Dec 13. PMID:30554841^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.