title: Membrane pore formation at protein-lipid interfaces.
abstract: Pore-forming proteins (PFPs) interact with lipid bilayers to compromise membrane integrity. Many PFPs function by inserting a ring of oligomerized subunits into the bilayer to form a protein-lined hydrophilic channel. However, mounting evidence suggests that PFPs can also generate 'proteolipidic' pores by contributing to the fusion of inner and outer bilayer leaflets to form a toroidal structure. We discuss here toroidal pore formation by peptides including melittin, protegrin, and Alzheimer's Aβ1-41, as well as by PFPs from several evolutionarily unrelated families: the colicin/Bcl-2 grouping including the pro-apoptotic protein Bax, actinoporins derived from sea anemones, and the membrane attack complex-perforin/cholesterol dependent cytolysin (MACPF/CDC) set of proteins. We also explore how the structure and biological role of toroidal pores might be investigated further.
authors.affiliation: Division of Structural Biology, Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Oxford OX3 7BN, UK. Electronic address: gilbert@strubi.ox.ac.uk.
authors.forename: Robert J C
authors.initials: RJ
authors.lastname: Gilbert
authors.affiliation: Consiglio Nazionale delle Ricerche, Istituto di Biofisica and Fondazione Bruno Kessler, Via alla Cascata 56/C, 38123, Trento, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Dalla Serra
authors.affiliation: NorthShore University Health Systems Research Institute and University of Chicago, Evanston, IL 60201, USA.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Froelich
authors.affiliation: Department of Chemistry, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, UK.
authors.forename: Mark I
authors.initials: MI
authors.lastname: Wallace
authors.affiliation: Department of Biology, Biotechnical Faculty, University of Ljubljana, Jamnikarjeva 101, 1000 Ljubljana, Slovenia; National Institute of Chemistry, Hajdrihova 19, 1000 Ljubljana, Slovenia. Electronic address: gregor.anderluh@ki.si.
authors.forename: Gregor
authors.initials: G
authors.lastname: Anderluh
mesh_terms: D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism; D003087:Colicins / Q000737:chemistry / Q000378:metabolism; D008051:Lipid Bilayers / Q000737:chemistry* / Q000378:metabolism; D008555:Melitten / Q000737:chemistry / Q000378:metabolism; D008563:Membrane Lipids / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D052899:Pore Forming Cytotoxic Proteins / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary
chemical_list: D003087:Colicins; D008051:Lipid Bilayers; D008563:Membrane Lipids; D052899:Pore Forming Cytotoxic Proteins; D008555:Melitten
keywords: Bcl-2/colicin family proteins; MACPF/CDC family proteins; actinoporins; pore-forming peptides and proteins; protein–membrane interactions; toroidal pore formation