NMR structure and dynamic studies of an anion-binding, channel-forming heptapeptide.
The synthetic peptide (C(18)H(37))(2)NCOCH(2)OCH(2)CON-(Gly)(3)-Pro-(Gly)(3)-OCH(2)Ph 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 CDCl(3) showed significant variation in the absence and presence of stoichiometric tetrabutylammonium chloride (Bu(4)NCl). 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.
Cook
Gabriel A
GA
Departments of Biochemistry and Chemistry, Kansas State University, Manhattan, Kansas 66506, USA.
Pajewski
Robert
R
Aburi
Mahalaxmi
M
Smith
Paul E
PE
Prakash
Om
O
Tomich
John M
JM
Gokel
George W
GW
D018118:Chloride Channels / Q000737:chemistry* / Q000378:metabolism; D002942:Circular Dichroism; D003198:Computer Simulation; D008051:Lipid Bilayers / Q000737:chemistry / Q000378:metabolism; D008081:Liposomes / Q000737:chemistry; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D011487:Protein Conformation
D018118:Chloride Channels; D008051:Lipid Bilayers; D008081:Liposomes; D009842:Oligopeptides