4wvm
From Proteopedia
Stonustoxin structure
Structural highlights
FunctionSTXA_SYNHO This lethal (towards mice) toxin induces hemolytic activities due to its ability to form pores in the cell membrane, elicits potent hypotension which is endothelium-dependent and appears to be mediated by the nitric oxide pathway and activation of potassium channels, displays edema-inducing activities, increases vascular permeability, induces endothelium-dependent vasorelaxation of isolated rat aorta, induces platelet aggregation, is myotoxic and interferes irreversibly with neuromuscular function.[1] [2] [3] Publication Abstract from PubMedThe 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 (alpha and beta), 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. Stonefish toxin defines an ancient branch of the perforin-like superfamily.,Ellisdon AM, Reboul CF, Panjikar S, Huynh K, Oellig CA, Winter KL, Dunstone MA, Hodgson WC, Seymour J, Dearden PK, Tweten RK, Whisstock JC, McGowan S Proc Natl Acad Sci U S A. 2015 Dec 1. pii: 201507622. PMID:26627714[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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