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| | <StructureSection load='2q0a' size='340' side='right'caption='[[2q0a]], [[Resolution|resolution]] 2.25Å' scene=''> | | <StructureSection load='2q0a' size='340' side='right'caption='[[2q0a]], [[Resolution|resolution]] 2.25Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2q0a]] is a 2 chain structure with sequence from [https://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=2Q0A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Q0A FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2q0a]] is a 2 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=2Q0A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2Q0A FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PCG:CYCLIC+GUANOSINE+MONOPHOSPHATE'>PCG</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]] 2.25Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Hcn2, Bcng2, Hac1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=PCG:CYCLIC+GUANOSINE+MONOPHOSPHATE'>PCG</scene></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=2q0a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q0a OCA], [https://pdbe.org/2q0a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2q0a RCSB], [https://www.ebi.ac.uk/pdbsum/2q0a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2q0a ProSAT]</span></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=2q0a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2q0a OCA], [https://pdbe.org/2q0a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2q0a RCSB], [https://www.ebi.ac.uk/pdbsum/2q0a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2q0a ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[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>
| + | [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: Flynn, G E]] | + | [[Category: Flynn GE]] |
| - | [[Category: Islas, L D]] | + | [[Category: Islas LD]] |
| - | [[Category: Sankaran, B]] | + | [[Category: Sankaran B]] |
| - | [[Category: Zagotta, W N]] | + | [[Category: Zagotta WN]] |
| - | [[Category: C-linker]]
| + | |
| - | [[Category: Cgmp]]
| + | |
| - | [[Category: Cyclic nucleotide binding domain]]
| + | |
| - | [[Category: Hcn2]]
| + | |
| - | [[Category: Ion channel]]
| + | |
| - | [[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
Hyperpolarization-activated cyclic nucleotide-modulated (HCN) ion channels regulate the spontaneous firing activity and electrical excitability of many cardiac and neuronal cells. The modulation of HCN channel opening by the direct binding of cAMP underlies many physiological processes such as the autonomic regulation of the heart rate. Here we use a combination of X-ray crystallography and electrophysiology to study the allosteric mechanism for cAMP modulation of HCN channels. SpIH is an invertebrate HCN channel that is activated fully by cAMP, but only partially by cGMP. We exploited the partial agonist action of cGMP on SpIH to reveal the molecular mechanism for cGMP specificity of many cyclic nucleotide-regulated enzymes. Our results also elaborate a mechanism for the allosteric conformational change in the cyclic nucleotide-binding domain and a mechanism for partial agonist action. These mechanisms will likely extend to other cyclic nucleotide-regulated channels and enzymes as well.
Structure and rearrangements in the carboxy-terminal region of SpIH channels.,Flynn GE, Black KD, Islas LD, Sankaran B, Zagotta WN Structure. 2007 Jun;15(6):671-82. PMID:17562314[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
- ↑ Flynn GE, Black KD, Islas LD, Sankaran B, Zagotta WN. Structure and rearrangements in the carboxy-terminal region of SpIH channels. Structure. 2007 Jun;15(6):671-82. PMID:17562314 doi:S0969-2126(07)00175-X
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