Direct cAMP Binding and PKA Phosphorylation Share a Common Gating Mechanism in HCN4 Channels
نویسندگان
چکیده
منابع مشابه
Phosphorylation and modulation of hyperpolarization-activated HCN4 channels by protein kinase A in the mouse sinoatrial node
The sympathetic nervous system increases heart rate by activating beta adrenergic receptors and increasing cAMP levels in myocytes in the sinoatrial node. The molecular basis for this response is not well understood; however, the cardiac funny current (I(f)) is thought to be among the end effectors for cAMP signaling in sinoatrial myocytes. I(f) is produced by hyperpolarization-activated cyclic...
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Backgroud: Protein-protein interaction, plays a key role in signal transduction in signaling pathways. Different approaches are used for prediction of these interactions including experimental and computational approaches. In conventional node-edge protein-protein interaction networks, we can only see which proteins interact but ‘structural networks’ show us how these proteins inter...
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Hyperpolarization-activated, cyclic nucleotide-sensitive (HCN) channels produce the I(f) and I(h) currents, which are critical for cardiac pacemaking and neuronal excitability, respectively. HCN channels are modulated by cyclic AMP (cAMP), which binds to a conserved cyclic nucleotide-binding domain (CNBD) in the C terminus. The unliganded CNBD has been shown to inhibit voltage-dependent gating ...
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Recent X-ray structures show that the binding domains of tetrameric ligand-gated channels form either a 4-fold symmetric gating ring or a 2-fold symmetric dimer of dimers. To determine how such structures function to coordinate the binding of multiple ligands during channel activation, we examined the action of cAMP to enhance the opening of the hyperpolarization-activated HCN2 channels, whose ...
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Based initially on their prominence in the squid giant axon, their useful pharmacology, and subsequently on being the first cloned K channels, voltage-gated K (Kv) channels have received the lion’s share of attention to their biophysical properties. Kv and Ca-activated K channel kinetics and gating mechanisms have been analyzed, and modeled, in exquisite detail (Hille, 2001). Inward rectifier K...
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ژورنال
عنوان ژورنال: Biophysical Journal
سال: 2012
ISSN: 0006-3495
DOI: 10.1016/j.bpj.2011.11.3673