title: Geometrical membrane curvature as an allosteric regulator of membrane protein structure and function.
abstract: Transmembrane proteins are embedded in cellular membranes of varied lipid composition and geometrical curvature. Here, we studied for the first time the allosteric effect of geometrical membrane curvature on transmembrane protein structure and function. We used single-channel optical analysis of the prototypic transmembrane β-barrel α-hemolysin (α-HL) reconstituted on immobilized single small unilamellar liposomes of different diameter and therefore curvature. Our data demonstrate that physiologically abundant geometrical membrane curvatures can enforce a dramatic allosteric regulation (1000-fold inhibition) of α-HL permeability. High membrane curvatures (1/diameter ~1/40 nm(-1)) compressed the effective pore diameter of α-HL from 14.2 ± 0.8 Å to 11.4 ± 0.6 Å. This reduction in effective pore area (~40%) when combined with the area compressibility of α-HL revealed an effective membrane tension of ~50 mN/m and a curvature-imposed protein deformation energy of ~7 kBT. Such substantial energies have been shown to conformationally activate, or unfold, β-barrel and α-helical transmembrane proteins, suggesting that membrane curvature could likely regulate allosterically the structure and function of transmembrane proteins in general.
authors.affiliation: Bionanotechnology and Nanomedicine Laboratory, Department of Chemistry, University of Copenhagen, Copenhagen, Denmark; Nano-Science Center, University of Copenhagen, Copenhagen, Denmark; Lundbeck Foundation Center for Biomembranes in Nanomedicine, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Asger
authors.initials: A
authors.lastname: Tonnesen
authors.affiliation: Bionanotechnology and Nanomedicine Laboratory, Department of Chemistry, University of Copenhagen, Copenhagen, Denmark; Nano-Science Center, University of Copenhagen, Copenhagen, Denmark; Lundbeck Foundation Center for Biomembranes in Nanomedicine, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Sune M
authors.initials: SM
authors.lastname: Christensen
authors.affiliation: Bionanotechnology and Nanomedicine Laboratory, Department of Chemistry, University of Copenhagen, Copenhagen, Denmark; Nano-Science Center, University of Copenhagen, Copenhagen, Denmark; Lundbeck Foundation Center for Biomembranes in Nanomedicine, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Vadym
authors.initials: V
authors.lastname: Tkach
authors.affiliation: Bionanotechnology and Nanomedicine Laboratory, Department of Chemistry, University of Copenhagen, Copenhagen, Denmark; Nano-Science Center, University of Copenhagen, Copenhagen, Denmark; Lundbeck Foundation Center for Biomembranes in Nanomedicine, University of Copenhagen, Copenhagen, Denmark. Electronic address: stamou@nano.ku.dk.
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Stamou
mesh_terms: D000494:Allosteric Regulation; D020816:Amino Acid Motifs; D002463:Cell Membrane Permeability; D006460:Hemolysin Proteins / Q000737:chemistry* / Q000378:metabolism; D008954:Models, Biological; D013211:Staphylococcus aureus / Q000737:chemistry; D053835:Unilamellar Liposomes / Q000737:chemistry* / Q000378:metabolism
chemical_list: D006460:Hemolysin Proteins; D053835:Unilamellar Liposomes