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

doi:10.1074/jbc.M114.572164

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

61 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
巻	289
号	32
DOI	https://doi.org/10.1074/jbc.M114.572164
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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10.1074/jbc.M114.572164

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引用スタイル

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AU - Selvaratnam, Rajeevan

AU - Van Schouwen, Bryan

AU - Gloyd, Melanie

AU - Accili, Eric A.

AU - Lange, Oliver F.

AU - Melacini, Giuseppe

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