Intracellular domains interactions and gated motions of IKS potassium channel subunits

Yoni Haitin, Reuven Wiener, Dana Shaham, Asher Peretz, Enbal Ben Tal Cohen, Liora Shamgar, Olaf Pongs, Joel A. Hirsch, Bernard Attali*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Voltage-gated K channels co-assemble with auxiliary Β subunits to form macromolecular complexes. In heart, assembly of Kv7.1 pore-forming subunits with KCNE1 Β 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.

Original languageEnglish
Pages (from-to)1994-2005
Number of pages12
JournalEMBO Journal
Volume28
Issue number14
DOIs
StatePublished - 22 Jul 2009

Keywords

  • Channel assembly
  • FRET
  • Gating
  • Kv7
  • Potassium channel

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