1q5o
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HCN2J 443-645 in the presence of cAMP, selenomethionine derivative
OverviewOverview
The family of hyperpolarization-activated, cyclic nucleotide-modulated, (HCN) channels are crucial for a range of electrical signalling, including, cardiac and neuronal pacemaker activity, setting resting membrane, electrical properties and dendritic integration. These nonselective cation, channels, underlying the I(f), I(h) and I(q) currents of heart and nerve, cells, are activated by membrane hyperpolarization and modulated by the, binding of cyclic nucleotides such as cAMP and cGMP. The cAMP-mediated, enhancement of channel activity is largely responsible for the increase in, heart rate caused by beta-adrenergic agonists. Here we have investigated, the mechanism underlying this modulation by studying a carboxy-terminal, fragment of HCN2 containing the cyclic nucleotide-binding domain (CNBD), and the C-linker region that connects the CNBD to the pore. X-ray, crystallographic structures of this C-terminal fragment bound to cAMP or, cGMP, together with equilibrium sedimentation analysis, identify a, tetramerization domain and the mechanism for cyclic nucleotide, specificity, and suggest a model for ligand-dependent channel modulation., On the basis of amino acid sequence similarity to HCN channels, the cyclic, nucleotide-gated, and eag- and KAT1-related families of channels are, probably related to HCN channels in structure and mechanism.
About this StructureAbout this Structure
1Q5O is a Single protein structure of sequence from Mus musculus with CMP as ligand. Full crystallographic information is available from OCA.
ReferenceReference
Structural basis for modulation and agonist specificity of HCN pacemaker channels., Zagotta WN, Olivier NB, Black KD, Young EC, Olson R, Gouaux E, Nature. 2003 Sep 11;425(6954):200-5. PMID:12968185
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