Peptide-lipid interactions and mechanisms of antimicrobial peptides.
Hydrophobic matching, in which transmembrane proteins cause the surrounding lipid bilayer to adjust its hydrocarbon thickness to match the length of the hydrophobic surface of the protein, is a commonly accepted idea. To test this idea, gramicidin was embedded in dilauroyl phosphatidylcholine (DLPC) and dimyristoyl phosphatidylcholine (DMPC) bilayers at the molar ratio 1:10. The bilayer thickness (PtP) was measured by X-ray lamellar diffraction. In the fluid phase near full hydration, PtP is 30.8 A for pure DLPC, 32.1 A for DLPC/gramicidin mixture, 35.3 A for pure DMPC and 32.7 A for a DMPC/gramicidin mixture. Gramicidin apparently stretches DLPC bilayers and thins DMPC bilayers toward a common thickness as expected by hydrophobic matching. Gramicidin pair correlations were measured by X-ray in-plane scattering. In the fluid phase, the gramicidin-gramicidin nearest-neighbour separation is 26.8 A in DLPC bilayers but shortens to 23.3 A in DMPC bilayers, thus confirming the conjecture that when proteins are embedded in a membrane, hydrophobic matching creates a strain field in the lipid bilayer that in turn gives rise to a membrane-mediated attractive potential between proteins. These results were analysed with an elasticity theory of membrane deformation. The same principle explains the 'concentration-gating' mechanism of pore formation by antimicrobial peptides via the membrane-thinning effect. Concentration-gated pore formation and membrane thinning by alamethicin and magainin have been observed.
Huang
H W
HW
Physics Department, Rice University, Houston, TX 77251-1892, USA.
D000900:Anti-Bacterial Agents / Q000737:chemistry*; D003198:Computer Simulation; D004734:Energy Metabolism / Q000502:physiology; D006096:Gramicidin / Q000737:chemistry*; D008051:Lipid Bilayers; D008565:Membrane Proteins / Q000737:chemistry*; D012995:Solubility; D014867:Water / Q000737:chemistry
D000900:Anti-Bacterial Agents; D008051:Lipid Bilayers; D008565:Membrane Proteins; D014867:Water; D006096:Gramicidin