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.
ASJC Scopus subject areas