Insights into the subunit arrangement and diversity of paradoxin and taipoxin

•Purification of paradoxin and taipoxin from whole snake venom.•Analysed the native state of these trimers using mass spectrometry.•Demonstrate that these toxins have similar architectures.•Reveal that paradoxin and taipoxin contain previously uncharacterised subunits.•Taipoxin exists as two distinct populations, due to multiple γ isoforms.

Paradoxin and taipoxin are neurotoxic phospholipases from the inland and coastal species of Australian taipan. Despite their relatively high sequence homology of 70% and 84% for the acidic and basic chains respectively, they differ substantially in reported assays of neurotoxicity. This study provides the first characterisation of paradoxin, which like taipoxin, is a trimer at physiological pH. More broadly, these toxins were found to be composed of a more diverse range of subunits than previously recognised, including newly discovered γTPx isoforms, which give rise to an additional, major conformation of TPx.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slide