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Stonefish toxin defines a new branch of the perforin‐like superfamily
Author(s) -
Ellisdon Andrew
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.lb194
Subject(s) - perforin , cytolysin , complement membrane attack complex , microbiology and biotechnology , biology , cytolysis , venom , immune system , genetics , gene , biochemistry , complement system , cytotoxic t cell , in vitro , virulence , cd8
The lethal factor in stonefish venom is Stonustoxin (SNTX), a cytolytic protein that induces hypotension and cardiovascular collapse in mammals. Here, we show that SNTX is a pore forming member of an undiscovered branch of the Cholesterol Dependent Cytolysin / Membrane Attack Complex/Perforin (CDC/MACPF) superfamily. Structural analyses suggest that the initial SNTX interaction with a target membrane is mediated by two C‐terminal PRYSPRY domains, which are closely related to the lipid and protein binding domains of the tripartite motif immune protein family. Two N‐terminal CDC/MACPF domains are arranged in a pre‐pore like assembly; these data provide high‐resolution insight into how SNTX and other CDC/MACPF proteins assemble into pores. Finally, our analyses reveal that SNTX‐like CDCs are distributed throughout eukaryotic life, and likely play a broader, and possibly immune‐related function, outside venom.