Distinct effects of disease-associated mutations in the proximal C-linker on negatively cooperative binding of cyclic nucleotides to the human HCN4 channel.

Abstract excerpt

The direct binding of cAMP to the hyperpolarization-activated cyclic nucleotide-gated channel form 4 (HCN4) protein contributes to autonomic modulation of heart rate. Here, we determine affinity for binding of cyclic nucleotides directly to the cytosolic C-terminus of the HCN4 channel of three disease-linked mutations that are found in the C-linker of the C-terminus, which attaches the more distal binding domain...

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