title: Structural restraints and heterogeneous orientation of the gramicidin A channel closed state in lipid bilayers.
abstract: Although there have been several decades of literature illustrating the opening and closing of the monovalent cation selective gramicidin A channel through single channel conductance, the closed conformation has remained poorly characterized. In sharp contrast, the open-state dimer is one of the highest resolution structures yet characterized in a lipid environment. To shift the open/closed equilibrium dramatically toward the closed state, a lower peptide/lipid molar ratio and, most importantly, long-chain lipids have been used. For the first time, structural evidence for a monomeric state has been observed for the native gramicidin A peptide. Solid-state NMR spectroscopy of single-site (15)N-labeled gramicidin in uniformly aligned bilayers in the L(alpha) phase have been observed. The results suggest a kinked structure with considerable orientational heterogeneity. The C-terminal domain is well structured, has a well-defined orientation in the bilayer, and appears to be in the bilayer interfacial region. On the other hand, the N-terminal domain, although appearing to be well structured and in the hydrophobic core of the bilayer, has a broad range of orientations relative to the bilayer normal. The structure is not just half of the open-state dimer, and neither is the structure restricted to the surface of the bilayer. Consequently, the monomeric or closed state appears to be a hybrid of these two models from the literature.
authors.affiliation: Department of Chemistry and Biochemistry and Institute of Molecular Biophysics, Florida State University, Tallahassee, Florida, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Mo
authors.forename: T A
authors.initials: TA
authors.lastname: Cross
authors.forename: W
authors.initials: W
authors.lastname: Nerdal
mesh_terms: D016880:Anisotropy; D000900:Anti-Bacterial Agents / Q000737:chemistry; D001703:Biophysics / Q000379:methods*; D019281:Dimerization; D006096:Gramicidin / Q000737:chemistry*; D006860:Hydrogen Bonding; D008051:Lipid Bilayers / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D009584:Nitrogen / Q000737:chemistry; D010455:Peptides / Q000737:chemistry; D011487:Protein Conformation; D017434:Protein Structure, Tertiary
chemical_list: D000900:Anti-Bacterial Agents; D008051:Lipid Bilayers; D010455:Peptides; D006096:Gramicidin; D009584:Nitrogen