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5-8 kDa pore-forming , antihistaminic ~20 kDa pore-forming Equinatoxins, sticholysins, tenebrosins, magnificalysins etc ~30-45 kDa pore-forming , PLA 2 activity 80 kDa pore-forming Metridiolysin (Metridium senile). Sea anemones produce a range of cytolytic peptides
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5-8 kDa pore-forming, antihistaminic • ~20 kDa pore-formingEquinatoxins, sticholysins, tenebrosins, magnificalysins etc • ~30-45 kDa pore-forming,PLA2 activity • 80 kDa pore-formingMetridiolysin (Metridium senile) • Sea anemones produce a range of cytolytic peptides • 4 primary groups: Sea Anemones Toxins
5-8 kDa pore-forming, antihistaminic • ~20 kDa pore-formingEquinatoxins, sticholysins, tenebrosins, magnificalysins etc actinoporins Sea Anemones Toxins 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) High sequence homology within the actinoporin family, common structural properties Equinatoxins Pores are formed by oligomers (tri- or tetramers) All monomeric, no Cys, rich in basic aminoacids
Sea Anemones Toxins From Actinia equina L. (European sea anemone) Equinatoxins EqtI EqtII EqtIII EqtIV EqtV
Equinatoxin II • b-Sandwich structure,2 a-helices on each side • N-terminal region (13-20) essential for cytolysis • Helix a1 is amphiphilic • Aromatic patch around W112 and W116, solvent-exposed
Equinatoxin II • b-Sandwich structure,2 a-helices on each side • N-terminal region (13-20) essential for cytolysis • Helix a1 is amphiphilic • Aromatic patch around W112 and W116, solvent-exposed
Equinatoxin II • b-Sandwich structure,2 a-helices on each side • N-terminal region (13-20) essential for cytolysis • Helix a1 is amphiphilic • Aromatic patch around W112 and W116, solvent-exposed
Equinatoxin II • b-Sandwich structure,2 a-helices on each side • N-terminal region (13-20) essential for cytolysis • Helix a1 is amphiphilic • Aromatic patch around W112 and W116, solvent-exposed
W112 StnII, EM @ 15 Å(Mancheño et al, 2003) Equinatoxin II • Interaction EqtII- Binding to the membrane No conformational change • Interaction EqtII-PC/ Insertion into the membrane Major conformational change • Insertion at raft boundary? • Role of Cholesterol? PC No poreReversible sphingomyeline Oligomerization (Tetramers) Irreversible
Equinatoxin II: Early Results 15 ns simulation helix 1 (N-terminal) helix 2 (C-terminal) Typ 112 Typ 116 POPC sphingomyeline (mini raft) (N-stearoylsphingomyeline) David Poger