Department of Anesthesiology

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The voltage-dependent gate in MthK potassium channels is located at the selectivity filter.

TitleThe voltage-dependent gate in MthK potassium channels is located at the selectivity filter.
Publication TypeJournal Article
Year of Publication2013
AuthorsPosson DJ, McCoy JG, Nimigean CM
JournalNat Struct Mol Biol
Volume20
Issue2
Pagination159-66
Date Published2013 Feb
ISSN1545-9985
KeywordsCrystallography, X-Ray, Ion Channel Gating, Kinetics, Methanobacterium, Models, Molecular, Potassium Channels, Voltage-Gated, Protein Conformation, Quaternary Ammonium Compounds
Abstract

Understanding how ion channels open and close their pores is crucial for comprehending their physiological roles. We used intracellular quaternary ammonium blockers, electrophysiology and X-ray crystallography to locate the voltage-dependent gate in MthK potassium channels from Methanobacterium thermoautotrophicum. Blockers bind in an aqueous cavity between two putative gates: an intracellular gate and the selectivity filter. Thus, these blockers directly probe gate location--an intracellular gate will prevent binding when closed, whereas a selectivity filter gate will always allow binding. Kinetic analysis of tetrabutylammonium block of single MthK channels combined with X-ray crystallographic analysis of the pore with tetrabutyl antimony unequivocally determined that the voltage-dependent gate, like the C-type inactivation gate in eukaryotic channels, is located at the selectivity filter. State-dependent binding kinetics suggest that MthK inactivation leads to conformational changes within the cavity and intracellular pore entrance.

DOI10.1038/nsmb.2473
Alternate JournalNat. Struct. Mol. Biol.
PubMed ID23262489
PubMed Central IDPMC3565016
Grant ListF32 GM087865 / GM / NIGMS NIH HHS / United States
F32GM087865 / GM / NIGMS NIH HHS / United States
R01 GM088352 / GM / NIGMS NIH HHS / United States
R01GM088352 / GM / NIGMS NIH HHS / United States