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| | <SX load='5u6p' size='340' side='right' viewer='molstar' caption='[[5u6p]], [[Resolution|resolution]] 3.51Å' scene=''> | | <SX load='5u6p' size='340' side='right' viewer='molstar' caption='[[5u6p]], [[Resolution|resolution]] 3.51Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5u6p]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5U6P OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5U6P FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5u6p]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5U6P OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5U6P 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">Electron Microscopy, [[Resolution|Resolution]] 3.51Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=UNK:UNKNOWN'>UNK</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></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5u6o|5u6o]]</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=5u6p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u6p OCA], [https://pdbe.org/5u6p PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5u6p RCSB], [https://www.ebi.ac.uk/pdbsum/5u6p PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5u6p ProSAT]</span></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HCN1, BCNG1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5u6p FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5u6p OCA], [http://pdbe.org/5u6p PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5u6p RCSB], [http://www.ebi.ac.uk/pdbsum/5u6p PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5u6p ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Disease == | | == Disease == |
| - | [[http://www.uniprot.org/uniprot/HCN1_HUMAN HCN1_HUMAN]] Early infantile epileptic encephalopathy. The disease is caused by mutations affecting the gene represented in this entry. | + | [https://www.uniprot.org/uniprot/HCN1_HUMAN HCN1_HUMAN] Early infantile epileptic encephalopathy. The disease is caused by mutations affecting the gene represented in this entry. |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/HCN1_HUMAN HCN1_HUMAN]] 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). May mediate responses to sour stimuli.<ref>PMID:15351778</ref> | + | [https://www.uniprot.org/uniprot/HCN1_HUMAN HCN1_HUMAN] 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). May mediate responses to sour stimuli.<ref>PMID:15351778</ref> |
| - | <div style="background-color:#fffaf0;">
| + | |
| - | == Publication Abstract from PubMed ==
| + | |
| - | Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels underlie the control of rhythmic activity in cardiac and neuronal pacemaker cells. In HCN, the polarity of voltage dependence is uniquely reversed. Intracellular cyclic adenosine monophosphate (cAMP) levels tune the voltage response, enabling sympathetic nerve stimulation to increase the heart rate. We present cryo-electron microscopy structures of the human HCN channel in the absence and presence of cAMP at 3.5 A resolution. HCN channels contain a K+ channel selectivity filter-forming sequence from which the amino acids create a unique structure that explains Na+ and K+ permeability. The voltage sensor adopts a depolarized conformation, and the pore is closed. An S4 helix of unprecedented length extends into the cytoplasm, contacts the C-linker, and twists the inner helical gate shut. cAMP binding rotates cytoplasmic domains to favor opening of the inner helical gate. These structures advance understanding of ion selectivity, reversed polarity gating, and cAMP regulation in HCN channels.
| + | |
| - | | + | |
| - | Structures of the Human HCN1 Hyperpolarization-Activated Channel.,Lee CH, MacKinnon R Cell. 2017 Jan 12;168(1-2):111-120.e11. doi: 10.1016/j.cell.2016.12.023. Epub, 2017 Jan 12. PMID:28086084<ref>PMID:28086084</ref>
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| - | | + | |
| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
| + | |
| - | </div>
| + | |
| - | <div class="pdbe-citations 5u6p" style="background-color:#fffaf0;"></div>
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| | | | |
| | ==See Also== | | ==See Also== |
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| | __TOC__ | | __TOC__ |
| | </SX> | | </SX> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lee, C H]] | + | [[Category: Lee C-H]] |
| - | [[Category: MacKinnon, R]] | + | [[Category: MacKinnon R]] |
| - | [[Category: Pacemaker ion channel]]
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| - | [[Category: Transport protein]]
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