Ion Selectivity in a Semisynthetic K + Channel Locked in the Conductive Conformation

Author:

Valiyaveetil Francis I.1,Leonetti Manuel1,Muir Tom W.1,MacKinnon Roderick1

Affiliation:

1. Laboratories of Molecular Neurobiology and Biophysics and Synthetic Protein Chemistry, Rockefeller University and Howard Hughes Medical Institute, 1230 York Avenue, New York, NY 10021, USA, and Department of Biology, Ecole Normale Superieure, 46 rue d'Ulm, 75005 Paris, France.

Abstract

Potassium channels are K + -selective protein pores in cell membrane. The selectivity filter is the functional unit that allows K + channels to distinguish potassium (K + ) and sodium (Na + ) ions. The filter's structure depends on whether K + or Na + ions are bound inside it. We synthesized a K + channel containing the d -enantiomer of alanine in place of a conserved glycine and found by x-ray crystallography that its filter maintains the K + (conductive) structure in the presence of Na + and very low concentrations of K + . This channel conducts Na + in the absence of K + but not in the presence of K + . These findings demonstrate that the ability of the channel to adapt its structure differently to K + and Na + is a fundamental aspect of ion selectivity, as is the ability of multiple K + ions to compete effectively with Na + for the conductive filter.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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