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Publication Abstract from PubMed

Cyclic AMP is thought to facilitate the opening of the HCN2 channel by binding to a C-terminal domain and promoting or inhibiting interactions between subunits. Here, we correlated the ability of cyclic nucleotides to promote interactions of isolated HCN2 C-terminal domains in solution with their ability to facilitate channel opening. Cyclic IMP, a cyclic purine nucleotide, and cCMP, a cyclic pyrimidine nucleotide, bind to a C-terminal domain containing the cyclic nucleotide-binding domain but, in contrast to other cyclic nucleotides examined, fail to promote its oligomerization, and produce only modest facilitation of opening of the full-length channel. Comparisons between ligand bound structures identify a region between the sixth and seventh beta strands and the distal C helix as important for facilitation and tight binding. We propose that promotion of interactions between the C-terminal domains by a given ligand contribute to its ability to facilitate opening of the full-length channel.

Cyclic Purine and Pyrimidine Nucleotides Bind to the HCN2 Ion Channel and Variably Promote C-Terminal Domain Interactions and Opening.,Ng LC, Putrenko I, Baronas V, Van Petegem F, Accili EA Structure. 2016 Aug 23. pii: S0969-2126(16)30193-9. doi:, 10.1016/j.str.2016.06.024. PMID:27568927^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.