Prev. Article Next Article Table of Contents

Article

NMR Structure and Dynamic Studies of an Anion-Binding, Channel-Forming Heptapeptide

Gabriel A. Cook,^† Robert Pajewski, Mahalaxmi Aburi,^† Paul E. Smith,^‡ Om Prakash,^† John M. Tomich,^† and George W. Gokel*^§

Contribution from the Departments of Biochemistry and Chemistry, Kansas State University, Manhattan, Kansas 66506, Department of Chemistry, Washington University, 1 Brookings Drive, St. Louis, Missouri 63130, and Department of Molecular Biology & Pharmacology, Washington University School of Medicine, Campus Box 8103, 660 S. Euclid Avenue, St. Louis, Missouri 63110

J. Am. Chem. Soc., 2006, 128 (5), pp 1633–1638

DOI: 10.1021/ja055887j

Publication Date (Web): January 12, 2006

†

Department of Biochemistry, Kansas State University.

Department of Molecular Biology & Pharmacology, Washington University School of Medicine.

‡

Department of Chemistry, Kansas State University.

In papers with more than one author, the asterisk indicates the name of the author to whom inquiries about the paper should be addressed.

Department of Chemistry, Washington University.

, ggokel@wustl.edu

Abstract

The synthetic peptide (C₁₈H₃₇)₂NCOCH₂OCH₂CON−(Gly)₃−Pro−(Gly)₃−OCH₂Ph forms chloride-selective channels in liposomes and exhibits voltage-gating properties in planar phospholipid bilayers. The peptide fragment of the channel is based on a conserved motif in naturally occurring chloride transporters. Membrane-anchoring residues at the N- and C-terminal ends augment the peptide. NMR spectra (1D and 2D) of the channel in CDCl₃ showed significant variation in the absence and presence of stoichiometric tetrabutylammonium chloride (Bu₄NCl). One-dimensional solution-state NMR titration studies combined with computational molecular simulation studies indicate that the peptide interacts with the salt as an ion pair and H-bonds chloride. To our knowledge, this is the first structural analysis of any synthetic anion-channel salt complex.