title: Gramicidin channels are internally gated.
abstract: Gramicidin channels are archetypal molecular subjects for solid-state NMR studies and investigations of single-channel or cation conductance. Until now, the transitions between on and off conductance states have been thought, based on multichannel studies, to represent monomer <--> dimer reactions. Here we use a single-molecule deposition method (vesicle fusion to a planar bilayer) to show that gramicidin dimer channels do not normally dissociate when conductance terminates. Furthermore, the observation of two 13C peaks in solid-state NMR indicates very stable dichotomous conformations for both the first and second peptide bonds in the monomers, and a two-dimensional chemical exchange spectrum with a 12-s mixing time demonstrates that the Val1 carbonyl conformations exchange slowly, with lifetimes of several seconds. It is proposed that gramicidin channels are gated by small conformational changes in the channel near the permeation pathway. These studies demonstrate how regulation of conformations governing closed <--> open transitions may be achieved and studied at the molecular level.
authors.affiliation: Department of Physiology and Developmental Biology, Brigham Young University, Provo, Utah, USA.
authors.forename: Tyson L
authors.initials: TL
authors.lastname: Jones
authors.forename: Riqiang
authors.initials: R
authors.lastname: Fu
authors.forename: Frederick
authors.initials: F
authors.lastname: Nielson
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Cross
authors.forename: David D
authors.initials: DD
authors.lastname: Busath
mesh_terms: D000818:Animals; D002417:Cattle; D004058:Diffusion; D006096:Gramicidin / Q000378:metabolism*; D015640:Ion Channel Gating / Q000502:physiology*; D008051:Lipid Bilayers / Q000378:metabolism; D008081:Liposomes / Q000378:metabolism; D008564:Membrane Potentials / Q000502:physiology; D008954:Models, Biological; D019906:Nuclear Magnetic Resonance, Biomolecular
chemical_list: D008051:Lipid Bilayers; D008081:Liposomes; D006096:Gramicidin
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