How does KCNE1 regulate the Kv7.1 potassium channel? Model-structure, mutations, and dynamics of the Kv7.1-KCNE1 complex

Yana Gofman, Simona Shats, Bernard Attali, Turkan Haliloglu, Nir Ben-Tal

Research output: Contribution to journalArticlepeer-review

Abstract

The voltage-gated potassium channel Kv7.1 and its auxiliary subunit KCNE1 are expressed in the heart and give rise to the major repolarization current. The interaction of Kv7.1 with the single transmembrane helix of KCNE1 considerably slows channel activation and deactivation, raises single-channel conductance, and prevents slow voltage-dependent inactivation. We built a Kv7.1-KCNE1 model-structure. The model-structure agrees with previous disulfide mapping studies and enables us to derive molecular interpretations of electrophysiological recordings that we obtained for two KCNE1 mutations. An elastic network analysis of Kv7.1 fluctuations in the presence and absence of KCNE1 suggests a mechanistic perspective on the known effects of KCNE1 on Kv7.1 function: slow deactivation is attributed to the low mobility of the voltage-sensor domains upon KCNE1 binding, abolishment of voltage-dependent inactivation could result from decreased fluctuations in the external vestibule, and amalgamation of the fluctuations in the pore region is associated with enhanced ion conductivity.

Original languageEnglish
Pages (from-to)1343-1352
Number of pages10
JournalStructure
Volume20
Issue number8
DOIs
StatePublished - 8 Aug 2012

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