Stonefish toxin defines an ancient branch of the perforin-like superfamily
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
Abstract
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.
Details
Original language | English |
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Pages (from-to) | 15360-15365 |
Number of pages | 6 |
Journal | Proceedings of the National Academy of Sciences of the United States of America : PNAS |
Volume | 112 |
Issue number | 50 |
Publication status | Published - Dec 2015 |
Peer-reviewed | Yes |
Externally published | Yes |
External IDs
Scopus | 84950159567 |
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