4WVM

Stonustoxin structure

Summary for 4WVM

• Entry DOI: 10.2210/pdb4wvm/pdb
• Descriptor: Stonustoxin subunit alpha, Stonustoxin subunit beta (2 entities in total)
• Functional Keywords: macpf cdc, membrane attack complex, perforin cholesterol dependent, cytolysin, venom, pry, spry, thioredoxin focal adhesion targeting, toxin
• Biological source: Synanceia horrida (Estuarine stonefish); More
• Cellular location: Secreted: Q98989 Q91453
• Total number of polymer chains: 2
• Total formula weight: 159139.21

Authors

Ellisdon, A.M.,Panjikar, S.,Whisstock, J.C.,McGowan, S. (deposition date: 2014-11-06, release date: 2015-12-02, Last modification date: 2023-12-27)

Primary citation

Ellisdon, A.M.,Reboul, C.F.,Panjikar, S.,Huynh, K.,Oellig, C.A.,Winter, K.L.,Dunstone, M.A.,Hodgson, W.C.,Seymour, J.,Dearden, P.K.,Tweten, R.K.,Whisstock, J.C.,McGowan, S.
Stonefish toxin defines an ancient branch of the perforin-like superfamily.
Proc.Natl.Acad.Sci.USA, 112:15360-15365, 2015

PubMed 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.

PubMed: 26627714
DOI: 10.1073/pnas.1507622112

Experimental method

X-RAY DIFFRACTION (3.1 Å)