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PDBsum entry 4wvm
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References listed in PDB file
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Key reference
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Title
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Stonefish toxin defines an ancient branch of the perforin-Like superfamily.
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Authors
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A.M.Ellisdon,
C.F.Reboul,
S.Panjikar,
K.Huynh,
C.A.Oellig,
K.L.Winter,
M.A.Dunstone,
W.C.Hodgson,
J.Seymour,
P.K.Dearden,
R.K.Tweten,
J.C.Whisstock,
S.Mcgowan.
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Ref.
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Proc Natl Acad Sci U S A, 2015,
112,
15360-15365.
[DOI no: ]
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PubMed id
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Abstract
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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.
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