Glycine as a d-amino acid surrogate in the K+-selectivity filter
- *Laboratory of Molecular Neurobiology and Biophysics and Howard Hughes Medical Institute, The Rockefeller University, Box 47, 1230 York Avenue, New York, NY 10021; and †Laboratory of Synthetic Protein Chemistry, The Rockefeller University, Box 223, 1230 York Avenue, New York, NY 10021
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Contributed by Roderick MacKinnon, October 20, 2004
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.
Footnotes
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↵ ‡ To whom correspondence may be addressed. E-mail: muirt{at}mail.rockefeller.edu or mackinn{at}mail.rockefeller.edu.
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Abbreviation: TEA+, tetraethylammonium.
- Copyright © 2004, The National Academy of Sciences
