1q5o: Difference between revisions
New page: left|200px<br /><applet load="1q5o" size="450" color="white" frame="true" align="right" spinBox="true" caption="1q5o, resolution 2.3Å" /> '''HCN2J 443-645 in the ... |
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[[Image:1q5o.jpg|left|200px]]<br /><applet load="1q5o" size=" | [[Image:1q5o.jpg|left|200px]]<br /><applet load="1q5o" size="350" color="white" frame="true" align="right" spinBox="true" | ||
caption="1q5o, resolution 2.3Å" /> | caption="1q5o, resolution 2.3Å" /> | ||
'''HCN2J 443-645 in the presence of cAMP, selenomethionine derivative'''<br /> | '''HCN2J 443-645 in the presence of cAMP, selenomethionine derivative'''<br /> | ||
==Overview== | ==Overview== | ||
The family of hyperpolarization-activated, cyclic nucleotide-modulated | 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 Structure== | ==About this Structure== | ||
1Q5O is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with CMP as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | 1Q5O is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with <scene name='pdbligand=CMP:'>CMP</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Q5O OCA]. | ||
==Reference== | ==Reference== | ||
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[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Black, K | [[Category: Black, K D.]] | ||
[[Category: Gouaux, J | [[Category: Gouaux, J E.]] | ||
[[Category: Olivier, N | [[Category: Olivier, N B.]] | ||
[[Category: Olson, R.]] | [[Category: Olson, R.]] | ||
[[Category: Young, E | [[Category: Young, E C.]] | ||
[[Category: Zagotta, W | [[Category: Zagotta, W N.]] | ||
[[Category: CMP]] | [[Category: CMP]] | ||
[[Category: c-linker]] | [[Category: c-linker]] | ||
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[[Category: pka]] | [[Category: pka]] | ||
''Page seeded by [http:// | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:36:12 2008'' | ||
Revision as of 15:36, 21 February 2008
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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 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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