Sea Anemones Toxins
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Transcript of Sea Anemones Toxins
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:
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
Equinatoxins
Sea Anemones Toxins
From Actinia equina L. (European sea anemone)
EqtI
EqtIIIEqtII
EqtIVEqtV
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
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
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
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
• 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
Equinatoxin II: Early Results
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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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