Sea Anemones Toxins
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Sea Anemones Toxins
I. 5-8 kDa pore-forming, antihistaminicII. ~20 kDa pore-forming
Equinatoxins, sticholysins, tenebrosins, magnificalysins etc
III. ~30-45 kDa pore-forming, PLA2 activityIV. 80 kDa pore-forming
Metridiolysin (Metridium senile)
• Sea anemones produce a range of cytolytic peptides• 4 primary groups:
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Sea Anemones Toxins
I. 5-8 kDa pore-forming, antihistaminicII. ~20 kDa pore-forming
Equinatoxins, sticholysins, tenebrosins, magnificalysins etc
actinoporins
Most numerous and most studied class:Equinatoxins II, IV and V (Actinia equina)Tenebrosins A, B and C (A. tenebrosa)Caritoxin (A. cari)Sticholysins StnI, StnII (Stichodactyla helianthus) and Smt (S. mertensii)Magnificalysins HgmIII, HetI and HetII (Heteractis magnifica)
Pores are formed by oligomers (tri- or tetramers)
High sequence homology within the actinoporin family, common structural properties
All monomeric, no Cys, rich in basic aminoacids
Equinatoxins
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Equinatoxins
Sea Anemones Toxins
From Actinia equina L. (European sea anemone)
EqtI
EqtIIIEqtII
EqtIVEqtV
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Equinatoxin II• -Sandwich structure,2 -helices on each side• N-terminal region (13-20) essential for cytolysis• Helix 1 is amphiphilic• Aromatic patch around W112 and W116, solvent-exposed
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Equinatoxin II• -Sandwich structure,2 -helices on each side• N-terminal region (13-20) essential for cytolysis• Helix 1 is amphiphilic• Aromatic patch around W112 and W116, solvent-exposed
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Equinatoxin II• -Sandwich structure,2 -helices on each side• N-terminal region (13-20) essential for cytolysis• Helix 1 is amphiphilic• Aromatic patch around W112 and W116, solvent-exposed
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Equinatoxin II• -Sandwich structure,2 -helices on each side• N-terminal region (13-20) essential for cytolysis• Helix 1 is amphiphilic• Aromatic patch around W112 and W116, solvent-exposed
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• Interaction EqtII-Binding to the membraneNo conformational change
• Interaction EqtII-PC/Insertion into the membrane Major conformational change
• Insertion at raft boundary? • Role of Cholesterol?
Equinatoxin II
StnII, EM @ 15 Å(Mancheño et al, 2003)
W112
PC
No poreReversible
sphingomyeline
Oligomerization (Tetramers) Irreversible
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Equinatoxin II: Early Results
QuickTime™ and a decompressor
are needed to see this picture.
15 ns simulation
sphingomyeline (mini raft)(N-stearoylsphingomyeline)
POPC
Typ 112
Typ 116
helix 1 (N-terminal)
helix 2 (C-terminal)
David Poger
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return