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Biophys J. 2014 Jan 7;106(1):201-9. doi: 10.1016/j.bpj.2013.11.023.

Geometrical membrane curvature as an allosteric regulator of membrane protein structure and function.

Author information

1
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.
2
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.

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.

PMID:
24411252
PMCID:
PMC3907227
DOI:
10.1016/j.bpj.2013.11.023
[Indexed for MEDLINE]
Free PMC Article

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