Glycine as a D-amino acid surrogate in the K(+)-selectivity filter.
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.
Valiyaveetil
Francis I
FI
Laboratory of Molecular Neurobiology and Biophysics and Howard Hughes Medical Institute, The Rockefeller University, Box 47, 1230 York Avenue, New York, NY 10021, USA.
Sekedat
Matthew
M
Mackinnon
Roderick
R
Muir
Tom W
TW
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
D015221:Potassium Channels; D000409:Alanine; D005998:Glycine