Glycine as a D-amino acid surrogate in the K+-selectivity filter

Francis I. Valiyaveetil, Matthew Sekedat, Roderick MacKinnon, Tom W. Muir

Research output: Contribution to journalArticlepeer-review

76 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)17045-17049
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number49
DOIs
StatePublished - Dec 7 2004
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General

Keywords

  • K channels
  • Semisynthesis

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