Direct Evidence for a Similar Molecular Mechanism Underlying Shaker Kv Channel Fast Inactivation and Clustering

Limor Lewin, Valerie Nirenberg, Rinat Yehezkel, Shany Naim, Uri Abdu, Irit Orr, Ofer Yifrach

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

The fast inactivation and clustering functions of voltage-dependent potassium channels play fundamental roles in electrical signaling. Recent evidence suggests that both these distinct channel functions rely on intrinsically disordered N- and C-terminal cytoplasmic segments that function as entropic clocks to time channel inactivation or scaffold protein-mediated clustering, both relying on what can be described as a “ball and chain” binding mechanism. Although the mechanisms employed in each case are seemingly analogous, both were put forward based on bulky chain deletions and further exhibit differences in reaction order. These considerations raised the question of whether the molecular mechanisms underlying Kv channel fast inactivation and clustering are indeed analogous. By taking a “chain”-level chimeric channel approach involving long and short spliced inactivation or clustering “chain” variants of the Shaker Kv channel, we demonstrate the ability of native inactivation and clustering “chains” to substitute for each other in a length-dependent manner, as predicted by the “ball and chain” mechanism. Our results thus provide direct evidence arguing that the two completely unrelated Shaker Kv channel processes of fast inactivation and clustering indeed occur according to a similar molecular mechanism.

Original languageEnglish
Pages (from-to)542-556
Number of pages15
JournalJournal of Molecular Biology
Volume431
Issue number3
DOIs
StatePublished - 1 Feb 2019

Keywords

  • Channel clustering
  • Entropic chains
  • Intrinsic disorder
  • PSD-95
  • “Ball and chain”

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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