Validation of the single-stranded channel conformation of gramicidin A by solid-state NMR

The monovalent cation selective channel formed by a dimer of the polypeptid e gramicidin A has a single-stranded, right-handed helical motif with 6.5 r esidues per turn forming a 4-Angstrom diameter pore. The structure has been refined to high resolution against 120 orientational constraints obtained from samples in a liquid-crystalline phase lipid bilayer, These structural constraints from solid-state NMP. reflect the orientation of spin interacti on tensors with respect to a unique molecular axis, Because these tensors a re fixed in the molecular frame and because the samples are uniformly align ed with respect to the magnetic field of the NMR spectrometer, each constra int restricts the orientation of internuclear vectors with respect to the l aboratory frame of reference. The structural motif of this channel has been validated, and the high-resolution structure has led to precise models for cation binding, cation selectivity, and cation conductance efficiency. The structure is consistent with the electrophysiological data and numerous bi ophysical studies.. Contrary to a recent claim [Burkhart, B. M., Li, N., La ngs, D.A., Pangborn, W. A. & Duax, W. L. (1998) Proc. Natl. Acad. Sci. USA 95, 12950-12955], the solid-state NMR constraints for gramicidin A in a lip id bilayer are not consistent with an x-ray crystallographic structure for gramicidin baring a double-stranded, right-handed helix with 7.2 residues p er turn.