Structural venomics reveals evolution of a complex venom by duplication and diversification of an ancient peptide-encoding gene

• DOI: 10.1073/pnas.1914536117
• Publication Date: 2020-05-12T20:55:14Z
• Authors: Sandy S. Pineda; Yanni K.-Y. Chin; Eivind A. B. Undheim; Sebastian Senff; Mehdi Mobli; Claire Dauly; Pierre Escoubas; Graham M. Nicholson; Quentin Kaas; Shaodong Guo; Volker Herzig; John S. Mattick; Glenn F. King
• Keywords: Proteome; Toxicogenomics

Spiders are one of the most successful venomous animals, with more than 48,000 described species. Most spider venoms dominated by cysteine-rich peptides a diverse range pharmacological activities. Some contain thousands unique peptides, but little is known about mechanisms used to generate such complex chemical arsenals. We an integrated transcriptomic, proteomic, and structural biology approach demonstrate that lethal Australian funnel-web produces 33 superfamilies venom proteins. Twenty-six disulfide-rich we show 15 these knottins contribute >90% proteome. NMR analyses revealed structurally related in complexity from simple highly elaborated knottin domains, as well double-knot toxins, likely evolved single ancestral toxin gene.