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EMBO J. 2009 Jul 22;28(14):1994-2005. doi: 10.1038/emboj.2009.157. Epub 2009 Jun 11.

Intracellular domains interactions and gated motions of I(KS) potassium channel subunits.

Author information

1
Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.

Abstract

Voltage-gated K(+) channels co-assemble with auxiliary beta subunits to form macromolecular complexes. In heart, assembly of Kv7.1 pore-forming subunits with KCNE1 beta subunits generates the repolarizing K(+) current I(KS). However, the detailed nature of their interface remains unknown. Mutations in either Kv7.1 or KCNE1 produce the life-threatening long or short QT syndromes. Here, we studied the interactions and voltage-dependent motions of I(KS) channel intracellular domains, using fluorescence resonance energy transfer combined with voltage-clamp recording and in vitro binding of purified proteins. The results indicate that the KCNE1 distal C-terminus interacts with the coiled-coil helix C of the Kv7.1 tetramerization domain. This association is important for I(KS) channel assembly rules as underscored by Kv7.1 current inhibition produced by a dominant-negative C-terminal domain. On channel opening, the C-termini of Kv7.1 and KCNE1 come close together. Co-expression of Kv7.1 with the KCNE1 long QT mutant D76N abolished the K(+) currents and gated motions. Thus, during channel gating KCNE1 is not static. Instead, the C-termini of both subunits experience molecular motions, which are disrupted by the D76N causing disease mutation.

PMID:
19521339
PMCID:
PMC2718281
DOI:
10.1038/emboj.2009.157
[Indexed for MEDLINE]
Free PMC Article

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