García Ortega, Lucía and Alegre Cebollada, Jorge and García Linares, Sara and Bruix, Marta and Martínez del Pozo, Álvaro and Gavilanes, José G. (2011) The behaviour of sea anemone actinoporins at the water-membrane interface. Biochimica et Biophysica Acta - Biomembranes, 1808 . pp. 2275-2288. ISSN 0005-2736
Actinoporins constitute a group of small and basic α-pore forming toxins produced by sea anemones. They display high sequence identity and appear as multigene families. They show a singular behaviour at the water-membrane interface: In aqueous solution, actinoporins remain stably folded but, upon interaction with lipid bilayers, become integral membrane structures. These membranes contain sphingomyelin, display phase coexistence, or both. The water soluble structures of the actinoporins equinatoxin II (EqtII) and sticholysin II (StnII) are known in detail. The crystalline structure of a fragaceatoxin C (FraC) nonamer has been also determined. The three proteins fold as a β-sandwich motif flanked by two α-helices, one of them at the N-terminal end. Four regions seem to be especially important: A cluster of aromatic residues, a phosphocholine binding site, an array of basic amino acids, and the N-terminal α-helix. Initial binding of the soluble monomers to the membrane is accomplished by the cluster of aromatic amino acids, the array of basic residues, and the phosphocholine binding site. Then, the N-terminal α-helix detaches from the β-sandwich, extends, and lies parallel to the membrane. Simultaneously, oligomerization occurs. Finally, the extended N-terminal α-helix penetrates the membrane to build a toroidal pore. This model has been however recently challenged by the cryo-EM reconstruction of FraC bound to phospholipid vesicles. Actinoporins structural fold appears across all eukaryotic kingdoms in other functionally unrelated proteins. Many of these proteins neither bind to lipid membranes nor induce cell lysis. Finally, studies focusing on the therapeutic potential of actinoporins also abound.
|Uncontrolled Keywords:||Actinoporin, Equinatoxin, Sticholysin, Membrane-pore, Pore-forming-toxin|
|Subjects:||Sciences > Chemistry > Biochemistry|
|Deposited On:||14 Jul 2011 10:14|
|Last Modified:||14 Jul 2011 10:14|
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