Structural Determinants of KvLQT1 Control by the KCNE Family of Proteins

Yonathan F. Melman, Anna Domènech, Susana De la Luna, Thomas V. McDonald

Research output: Contribution to journalArticle

86 Scopus citations

Abstract

KvLQT1 is a Shaker-like voltage-gated potassium channel that when complexed with minK (KCNE1) produces the slowly activating delayed rectifier Iks. The emerging family of KCNE1-related peptides includes KCNE1 and KCNE3, both of which complex with KvLQT1 to produce functionally distinct currents. Namely Iks, the slowly activating delayed rectifier current, is produced by KvLQT1/KCNE1, whereas KvLQT1/KCNE3 yields a more rapidly activating current with a distinct constitutively active component. We exploited these functional differences and the general structural similarities of KCNE1 and KCNE3 to study which physical regions are critical for control of KvLQT1 by making chimerical constructs of KCNE1 and KCNE3. By using this approach, we have found that a three-amino acid stretch within the transmembrane domain is necessary and sufficient to confer specificity of control of activation kinetics by KCNE1 and KCNE3. Moreover, chimera analysis showed that different regions within the transmembrane domain control deactivation rates. Our results help to provide a basis for understanding the mechanism by which KCNE proteins control K+ channel activity.

Original languageEnglish (US)
Pages (from-to)6439-6444
Number of pages6
JournalJournal of Biological Chemistry
Volume276
Issue number9
DOIs
StatePublished - Mar 2 2001

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Melman, Y. F., Domènech, A., De la Luna, S., & McDonald, T. V. (2001). Structural Determinants of KvLQT1 Control by the KCNE Family of Proteins. Journal of Biological Chemistry, 276(9), 6439-6444. https://doi.org/10.1074/jbc.M010713200