Department of Anesthesiology

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Mechanism of potassium-channel selectivity revealed by Na(+) and Li(+) binding sites within the KcsA pore.

TitleMechanism of potassium-channel selectivity revealed by Na(+) and Li(+) binding sites within the KcsA pore.
Publication TypeJournal Article
Year of Publication2009
AuthorsThompson AN, Kim I, Panosian TD, Iverson TM, Allen TW, Nimigean CM
JournalNat Struct Mol Biol
Volume16
Issue12
Pagination1317-24
Date Published2009 Dec
ISSN1545-9985
KeywordsBacterial Proteins, Binding Sites, Cations, Crystallography, X-Ray, Electricity, Lithium, Molecular Dynamics Simulation, Potassium, Potassium Channels, Protein Structure, Tertiary, Sodium, Streptomyces lividans, Substrate Specificity
Abstract

Potassium channels allow K(+) ions to diffuse through their pores while preventing smaller Na(+) ions from permeating. Discrimination between these similar, abundant ions enables these proteins to control electrical and chemical activity in all organisms. Selection occurs at the narrow selectivity filter containing structurally identified K(+) binding sites. Selectivity is thought to arise because smaller ions such as Na(+) do not bind to these K(+) sites in a thermodynamically favorable way. Using the model K(+) channel KcsA, we examined how intracellular Na(+) and Li(+) interact with the pore and the permeant ions using electrophysiology, molecular dynamics simulations and X-ray crystallography. Our results suggest that these small cations have a separate binding site within the K(+) selectivity filter. We propose that selective permeation from the intracellular side primarily results from a large energy barrier blocking filter entry for Na(+) and Li(+) in the presence of K(+), not from a difference of binding affinity between ions.

DOI10.1038/nsmb.1703
Alternate JournalNat. Struct. Mol. Biol.
PubMed ID19946269
PubMed Central IDPMC2825899
Grant List1-T32-NS07491-06 / NS / NINDS NIH HHS / United States
5-R01-GM079419-03 / GM / NIGMS NIH HHS / United States
5-T32-GM008320-19 / GM / NIGMS NIH HHS / United States
GM077560 / GM / NIGMS NIH HHS / United States
R01 GM077560-01A1 / GM / NIGMS NIH HHS / United States
R01 GM079419-04 / GM / NIGMS NIH HHS / United States
R01 GM088352-02 / GM / NIGMS NIH HHS / United States