Abstract
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.
Original language | English (US) |
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Pages (from-to) | 22205-22220 |
Number of pages | 16 |
Journal | Journal of Biological Chemistry |
Volume | 289 |
Issue number | 32 |
DOIs | |
State | Published - Aug 8 2014 |