Publication: Sea anemone actinoporins: The transition from a folded soluble state to a functionally active membrane-bound oligomeric pore
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Publication Date
2007-12
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Abstract
Actinoporins are a family of 20-kDa, basic proteins isolated from sea anemones, whose activity is inhibited by
preincubation with sphingomyelin. They are produced in monomeric soluble form but, when binding to the plasma membrane,
they oligomerize to produce functional pores which result in cell lysis. Equinatoxin II (EqtII) from Actinia equina
and Sticholysin II (StnII) from Stichodactyla helianthus are the actinoporins that have been studied in more detail. Both
proteins display a beta-sandwich fold composed of 10 beta-strands flanked on each side by two short alpha-helices. Twodimensional
crystallization on lipid monolayers has allowed the determination of low-resolution models of tetrameric
structures distinct from the pore. However, the actual structure of the pore is not known yet. Wild-type EqtII and StnII, as
well as a nice collection of natural and artificially made variants of both proteins, have been produced in Escherichia coli
and purified. Their characterization has allowed the proposal of a model for the mechanism of pore formation. Four regions
of the actinoporins structure seem to play an important role. First, a phosphocholine-binding site and a cluster of exposed
aromatic residues, together with a basic region, would be involved in the initial interaction with the membrane,
whereas the amphipathic N-terminal region would be essential for oligomerization and pore formation. Accordingly, the
model states that pore formation would proceed in at least four steps: Monomer binding to the membrane interface, assembly
of four monomers, and at least two distinct conformational changes driving to the final formation of the functional
pore.