title: Protein stability and conformational rearrangements in lipid bilayers: linear gramicidin, a model system.
abstract: The replacement of four tryptophans in gramicidin A by four phenylalanines (gramicidin M) causes no change in the molecular fold of this dimeric peptide in a low dielectric isotropic organic solvent, but the molecular folds are dramatically different in a lipid bilayer environment. The indoles of gramicidin A interact with the anisotropic bilayer environment to induce a change in the molecular fold. The double-helical fold of gramicidin M, as opposed to the single-stranded structure of gramicidin A, is not compatible with ion conductance. Gramicidin A/gramicidin M hybrid structures have also been prepared, and like gramicidin M homodimers, these dimeric hybrids appear to have a double-helical fold, suggesting that a couple of indoles are being buried in the bilayer interstices. To achieve this equilibrium structure (i.e., minimum energy conformation), incubation at 68 degrees C for 2 days is required. Kinetically trapped metastable structures may be more common in lipid bilayers than in an aqueous isotropic environment. Structural characterizations in the bilayers were achieved with solid-state NMR-derived orientational constraints from uniformly aligned lipid bilayer samples, and characterizations in organic solvents were accomplished by solution NMR.
authors.affiliation: Center for Interdisciplinary Magnetic Resonance, National High Magnetic Field Laboratory, Tallahassee, FL 32306-4005, USA.
authors.forename: M
authors.initials: M
authors.lastname: Cotten
authors.forename: F
authors.initials: F
authors.lastname: Xu
authors.forename: T A
authors.initials: TA
authors.lastname: Cross
mesh_terms: D019281:Dimerization; D004355:Drug Stability; D006096:Gramicidin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry*; D008051:Lipid Bilayers; D009682:Magnetic Resonance Spectroscopy; D011487:Protein Conformation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry*; D012997:Solvents; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D008051:Lipid Bilayers; D011506:Proteins; D012997:Solvents; D006096:Gramicidin; C036306:gramicidin A, 15-des-Trp-Phe-