title: Glycine as a D-amino acid surrogate in the K(+)-selectivity filter.
abstract: The K(+) channel-selectivity filter consists of two absolutely conserved glycine residues. Crystal structures show that the first glycine in the selectivity filter, Gly-77 in KcsA, is in a left-handed helical conformation. Although the left-handed helical conformation is not favorable for the naturally occurring L-amino acids, it is favorable for the chirally opposite D-amino acids. Here, we demonstrate that Gly-77 can be replaced by D-Ala with almost complete retention of function. In contrast, substitution with an L-amino acid results in a nonfunctional channel. This finding suggests that glycine is used as a surrogate D-amino acid in the selectivity filter. The absolute conservation of glycine in the K(+)-selectivity filter can be explained as a result of glycine being the only natural amino acid that can play this role.
authors.affiliation: Laboratory of Molecular Neurobiology and Biophysics and Howard Hughes Medical Institute, The Rockefeller University, Box 47, 1230 York Avenue, New York, NY 10021, USA.
authors.forename: Francis I
authors.initials: FI
authors.lastname: Valiyaveetil
authors.forename: Matthew
authors.initials: M
authors.lastname: Sekedat
authors.forename: Roderick
authors.initials: R
authors.lastname: Mackinnon
authors.forename: Tom W
authors.initials: TW
authors.lastname: Muir
mesh_terms: D000409:Alanine; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D004594:Electrophysiology; D005998:Glycine / Q000737:chemistry*; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D015221:Potassium Channels / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D015221:Potassium Channels; D000409:Alanine; D005998:Glycine