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A novel mechanism of pore formation: Membrane penetration by the N-terminal amphipathic region of equinatoxin

Lookup NU author(s): Professor Jeremy Lakey

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Abstract

Equinatoxin II is a representative of actinoporins, eukaryotic pore-forming toxins from sea anemones. It creates pores in natural and artificial lipid membranes by an association of three or four monomers. Cysteine-scanning mutagenesis was used to study the structure of the N terminus, which is proposed to be crucial in transmembrane pore formation. We provide data for two steps of pore formation: a lipid-bound monomeric intermediate state and a final oligomeric pore. Results show that residues 10-28 are organized as an α-helix in both steps. In the first step, the whole region is transferred to a lipid-water interface, laying flat on the membrane. In the pore-forming state, the hydrophilic side of the amphipathic helix lines the pore lumen. The pore has a restriction around Asp-10, according to the permeabilization ratio of ions flowing through pores formed by chemically modified mutants. A general model was introduced to derive the tilt angle of the helix from the ion current data. This study reveals that actinoporins use a unique single helix insertion mechanism for pore formation.


Publication metadata

Author(s): Malovrh P, Viero G, Dalla Serra M, Podlesek Z, Lakey JH, Macek P, Menestrina G, Anderluh G

Publication type: Article

Publication status: Published

Journal: Journal of Biological Chemistry

Year: 2003

Volume: 278

Issue: 25

Pages: 22678-22685

ISSN (print): 0021-9258

ISSN (electronic): 1083-351X

Publisher: American Society for Biochemistry and Molecular Biology, Inc.

URL: http://dx.doi.org/10.1074/jbc.M300622200

DOI: 10.1074/jbc.M300622200

PubMed id: 12676945


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