Functional truncated membrane pores.
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 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.
Department of Chemistry, University of Oxford, Oxford OX1 3TA, United Kingdom.
David
D
Stoddart
Mariam
M
Ayub
Lajos
L
Höfler
Pinky
P
Raychaudhuri
Jochen W
JW
Klingelhoefer
Giovanni
G
Maglia
Andrew
A
Heron
Hagan
H
Bayley
D001427:Bacterial Toxins / Q000737:chemistry / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000502:physiology*; D006460:Hemolysin Proteins / Q000737:chemistry / Q000378:metabolism; D008051:Lipid Bilayers / Q000737:chemistry* / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry* / Q000145:classification / Q000378:metabolism; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D016296:Mutagenesis; D016133:Polymerase Chain Reaction; D011487:Protein Conformation
D001427:Bacterial Toxins; D006460:Hemolysin Proteins; D008051:Lipid Bilayers; D008565:Membrane Proteins; C021091:staphylococcal alpha-toxin
alpha-hemolysin; beta-barrel; lipid reorganization; nanopore