The objectives of this project are to: (1) investigate the interaction of alcohol with proteins and lipids in biological membranes; (2) study structure and dynamics of membranes composed of lipids with polyunsaturated fatty acids such as docosahexaenoic acid (DHA, 22:6n-3); and (3) study lipid-protein interactions related to alcoholism and lipid polyunsaturation. (1) The location of ethanol within a membrane has been investigated directly with two-dimensional NOESY and magic-angle-spinning NMR. From NOESY crosspeak intensities we determined that ethanol resides with highest probability at the lipid-water interface near the lipid glycerol and the upper methylene segments of lipid hydrocarbon chains. Ethanol concentration in the bilayer hydrophobic core is significantly lower. (2) (2)H NMR spectroscopy was used to measure order in PCs with a perdeuterated stearoyl sn-1 chain and four unsaturated sn-2 chains - 18:1n-9, 18:2n-6, 20:4n-6, and 22:6n-3 - combined with PE of identical fatty acid composition and cholesterol. The polyunsaturated bilayers are distinct from the mono- and diunsaturated bilayers in that they had the lowest order at all cholesterol concentrations and were the least ordered by PE. Polyunsaturated membranes show less ethanol-induced chain disorder than mono- and diunsaturated membranes. A modified (17)O NMR method has been developed for measurement of fast water permeation through lipid bilayers. The lower hydrocarbon chain order in polyunsaturated lipids appears to correlate with higher water permeation rates through polyunsaturated membranes. Addition of ethanol reduces water permeation, most likely by restricting entry of water molecules into the membrane. (3) The peptide fragment 828-848 with the sequence RVIEVVQGACRAIRHIPRRIR from the carboxy terminal region of the envelope glycoprotein gp41 of HIV-1 deeply incorporates into negatively charged DMPC bilayers as an amphipathic alpha-helix. Measurements on peptide with specifically deuterated isoleucine amino acids demonstrate that three of the four isoleucine residues are deeply imbedded in the hydrocarbon core of the membrane. The positively charged carboxy terminus of the peptide is located at the bilayer surface and shows a higher degree of flexibility.
| Teague Jr, Walter E; Soubias, Olivier; Petrache, Horia et al. (2013) Elastic properties of polyunsaturated phosphatidylethanolamines influence rhodopsin function. Faraday Discuss 161:383-95; discussion 419-59 |
| Gawrisch, Klaus (2012) Tafazzin senses curvature. Nat Chem Biol 8:811-2 |
| Kimura, Tomohiro; Cheng, Kejun; Rice, Kenner C et al. (2009) Location, structure, and dynamics of the synthetic cannabinoid ligand CP-55,940 in lipid bilayers. Biophys J 96:4916-24 |
| Polozov, Ivan V; Bezrukov, Ludmila; Gawrisch, Klaus et al. (2008) Progressive ordering with decreasing temperature of the phospholipids of influenza virus. Nat Chem Biol 4:248-55 |
| Klauda, Jeffery B; Eldho, Nadukkudy V; Gawrisch, Klaus et al. (2008) Collective and noncollective models of NMR relaxation in lipid vesicles and multilayers. J Phys Chem B 112:5924-9 |
| Soubias, Olivier; Niu, Shui-Lin; Mitchell, Drake C et al. (2008) Lipid-rhodopsin hydrophobic mismatch alters rhodopsin helical content. J Am Chem Soc 130:12465-71 |
| Grossfield, Alan; Pitman, Michael C; Feller, Scott E et al. (2008) Internal hydration increases during activation of the G-protein-coupled receptor rhodopsin. J Mol Biol 381:478-86 |
| Gawrisch, Klaus; Soubias, Olivier (2008) Structure and dynamics of polyunsaturated hydrocarbon chains in lipid bilayers-significance for GPCR function. Chem Phys Lipids 153:64-75 |
| Soubias, Olivier; Gawrisch, Klaus (2007) Nuclear magnetic resonance investigation of oriented lipid membranes. Methods Mol Biol 400:77-88 |
| Krepkiy, Dmitriy; Gawrisch, Klaus; Yeliseev, Alexei (2007) Expression and purification of CB2 for NMR studies in micellar solution. Protein Pept Lett 14:1031-7 |
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