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Functional truncated membrane pores.

ABSTRACT: Membrane proteins are generally divided into two classes. Integral proteins span the lipid bilayer, and peripheral proteins are located at the membrane surface. Here, we provide evidence for membrane proteins of a third class that stabilize lipid pores, most probably as toroidal structures. We examined mutants of the staphylococcal ?-hemolysin pore so severely truncated that the protein cannot span a bilayer. Nonetheless, the doughnut-like structures elicited well-defined transmembrane ionic currents by inducing pore formation in the underlying lipids. The formation of lipid pores, produced here by a structurally defined protein, is supported by the lipid and voltage dependences of pore formation, and by molecular dynamics simulations. We discuss the role of stabilized lipid pores in amyloid disease, the action of antimicrobial peptides, and the assembly of the membrane-attack complexes of the immune system.

SUBMITTER: Stoddart D

PROVIDER: S-EPMC3932856 | biostudies-literature | 2014 Feb

REPOSITORIES: biostudies-literature

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Functional truncated membrane pores.

Stoddart David D Ayub Mariam M Höfler Lajos L Raychaudhuri Pinky P Klingelhoefer Jochen W JW Maglia Giovanni G Heron Andrew A Bayley Hagan H

Proceedings of the National Academy of Sciences of the United States of America 20140127 7

Membrane proteins are generally divided into two classes. Integral proteins span the lipid bilayer, and peripheral proteins are located at the membrane surface. Here, we provide evidence for membrane proteins of a third class that stabilize lipid pores, most probably as toroidal structures. We examined mutants of the staphylococcal α-hemolysin pore so severely truncated that the protein cannot span a bilayer. Nonetheless, the doughnut-like structures elicited well-defined transmembrane ionic cur ...[more]

PMID: 24469792

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