Stonefish toxin defines an ancient branch of the perforin-like superfamily

Research output: Contribution to journalResearch articleContributedpeer-review


  • Andrew Ellisdon - (Author)
  • Cyril F Reboul - (Author)
  • Santosh Panjikar - (Author)
  • Kitmun Huynh - (Author)
  • Christine A Oellig - , Monash University (Author)
  • Kelly L Winter - (Author)
  • Michelle A Dunstone - (Author)
  • Wayne C Hodgson - (Author)
  • Jamie Seymour - (Author)
  • Peter K Dearden - (Author)
  • Rodney K Tweten - (Author)
  • James C Whisstock - (Author)
  • Sheena McGowan - (Author)


The lethal factor in stonefish venom is stonustoxin (SNTX), a heterodimeric cytolytic protein that induces cardiovascular collapse in humans and native predators. Here, using X-ray crystallography, we make the unexpected finding that SNTX is a pore-forming member of an ancient branch of the Membrane Attack Complex-Perforin/Cholesterol-Dependent Cytolysin (MACPF/CDC) superfamily. SNTX comprises two homologous subunits (α and β), each of which comprises an N-terminal pore-forming MACPF/CDC domain, a central focal adhesion-targeting domain, a thioredoxin domain, and a C-terminal tripartite motif family-like PRY SPla and the RYanodine Receptor immune recognition domain. Crucially, the structure reveals that the two MACPF domains are in complex with one another and arranged into a stable early prepore-like assembly. These data provide long sought after near-atomic resolution insights into how MACPF/CDC proteins assemble into prepores on the surface of membranes. Furthermore, our analyses reveal that SNTX-like MACPF/CDCs are distributed throughout eukaryotic life and play a broader, possibly immune-related function outside venom.


Original languageEnglish
Pages (from-to)15360-15365
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America : PNAS
Issue number50
Publication statusPublished - Dec 2015
Externally publishedYes

External IDs

Scopus 84950159567