A mechanism for the auto-inhibition of hyperpolarization-activated cyclic nucleotide-gated (HCN) channel opening and its relief by cAMP

Madoka Akimoto, Zaiyong Zhang, Stephen Boulton, Rajeevan Selvaratnam, Bryan Van Schouwen, Melanie Gloyd, Eric A. Accili, Oliver F. Lange, Giuseppe Melacini

研究成果: Article査読

59 被引用数 (Scopus)

抄録

Background: Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels control electrical activity through tetramerization of an intracellular linker. Results: NMR shows that the apo-cAMP-binding domain (CBD) of HCN4 destabilizes the tetramer through steric clashes. Conclusion: The apo-HCN4 CBD structure is compatible with monomeric and dimeric but not with tetrameric HCN4. Significance: The proposed mechanism explains HCN auto-inhibition and its relaxation by cAMP.

本文言語English
ページ(範囲)22205-22220
ページ数16
ジャーナルJournal of Biological Chemistry
289
32
DOI
出版ステータスPublished - 2014 8月 8
外部発表はい

ASJC Scopus subject areas

  • 生化学
  • 分子生物学
  • 細胞生物学

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