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| | <StructureSection load='1q5o' size='340' side='right'caption='[[1q5o]], [[Resolution|resolution]] 2.30Å' scene=''> | | <StructureSection load='1q5o' size='340' side='right'caption='[[1q5o]], [[Resolution|resolution]] 2.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1q5o]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Q5O OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=1Q5O FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1q5o]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1Q5O OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1Q5O FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CMP:ADENOSINE-3,5-CYCLIC-MONOPHOSPHATE'>CMP</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.3Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CMP:ADENOSINE-3,5-CYCLIC-MONOPHOSPHATE'>CMP</scene>, <scene name='pdbligand=MSE:SELENOMETHIONINE'>MSE</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1q3e|1q3e]], [[1q43|1q43]]</div></td></tr>
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1q5o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1q5o OCA], [https://pdbe.org/1q5o PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1q5o RCSB], [https://www.ebi.ac.uk/pdbsum/1q5o PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1q5o ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HCN2, BCNG2 OR HAC1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr>
| + | |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=1q5o FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1q5o OCA], [http://pdbe.org/1q5o PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1q5o RCSB], [http://www.ebi.ac.uk/pdbsum/1q5o PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1q5o ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/HCN2_MOUSE HCN2_MOUSE]] Hyperpolarization-activated ion channel exhibiting weak selectivity for potassium over sodium ions. Contributes to the native pacemaker currents in heart (If) and in neurons (Ih). Can also transport ammonium in the distal nephron. Produces a large instantaneous current. Activated by cAMP. Modulated by intracellular chloride ions and pH; acidic pH shifts the activation to more negative voltages.<ref>PMID:11741901</ref> | + | [https://www.uniprot.org/uniprot/HCN2_MOUSE HCN2_MOUSE] Hyperpolarization-activated ion channel exhibiting weak selectivity for potassium over sodium ions. Contributes to the native pacemaker currents in heart (If) and in neurons (Ih). Can also transport ammonium in the distal nephron. Produces a large instantaneous current. Activated by cAMP. Modulated by intracellular chloride ions and pH; acidic pH shifts the activation to more negative voltages.<ref>PMID:11741901</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Black, K D]] | + | [[Category: Black KD]] |
| - | [[Category: Gouaux, J E]] | + | [[Category: Gouaux JE]] |
| - | [[Category: Olivier, N B]] | + | [[Category: Olivier NB]] |
| - | [[Category: Olson, R]] | + | [[Category: Olson R]] |
| - | [[Category: Young, E C]] | + | [[Category: Young EC]] |
| - | [[Category: Zagotta, W N]] | + | [[Category: Zagotta WN]] |
| - | [[Category: C-linker]]
| + | |
| - | [[Category: Camp]]
| + | |
| - | [[Category: Cap]]
| + | |
| - | [[Category: Channel]]
| + | |
| - | [[Category: Cnbd]]
| + | |
| - | [[Category: Cyclic nucleotide]]
| + | |
| - | [[Category: Hcn]]
| + | |
| - | [[Category: Hcn2]]
| + | |
| - | [[Category: Ion channel]]
| + | |
| - | [[Category: Ligand]]
| + | |
| - | [[Category: Pacemaker]]
| + | |
| - | [[Category: Pka]]
| + | |
| - | [[Category: Transport protein]]
| + | |
| Structural highlights
Function
HCN2_MOUSE Hyperpolarization-activated ion channel exhibiting weak selectivity for potassium over sodium ions. Contributes to the native pacemaker currents in heart (If) and in neurons (Ih). Can also transport ammonium in the distal nephron. Produces a large instantaneous current. Activated by cAMP. Modulated by intracellular chloride ions and pH; acidic pH shifts the activation to more negative voltages.[1]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
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.
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[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Proenza C, Angoli D, Agranovich E, Macri V, Accili EA. Pacemaker channels produce an instantaneous current. J Biol Chem. 2002 Feb 15;277(7):5101-9. Epub 2001 Dec 7. PMID:11741901 doi:http://dx.doi.org/10.1074/jbc.M106974200
- ↑ Zagotta WN, Olivier NB, Black KD, Young EC, Olson R, Gouaux E. Structural basis for modulation and agonist specificity of HCN pacemaker channels. Nature. 2003 Sep 11;425(6954):200-5. PMID:12968185 doi:http://dx.doi.org/10.1038/nature01922
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