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| | ==Tetramerization dynamics of the C-terminus underlies isoform-specific cAMP-gating in HCN channels== | | ==Tetramerization dynamics of the C-terminus underlies isoform-specific cAMP-gating in HCN channels== |
| - | <StructureSection load='3u0z' size='340' side='right' caption='[[3u0z]], [[Resolution|resolution]] 2.90Å' scene=''> | + | <StructureSection load='3u0z' size='340' side='right'caption='[[3u0z]], [[Resolution|resolution]] 2.90Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[3u0z]] is a 2 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=3U0Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3U0Z FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[3u0z]] 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=3U0Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3U0Z FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><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]] 2.9Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1q43|1q43]], [[3otf|3otf]], [[3u10|3u10]], [[3u11|3u11]]</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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Hcn1, Bcng1, Hac2 ([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'>[https://proteopedia.org/fgij/fg.htm?mol=3u0z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3u0z OCA], [https://pdbe.org/3u0z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3u0z RCSB], [https://www.ebi.ac.uk/pdbsum/3u0z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3u0z ProSAT]</span></td></tr> |
| - | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3u0z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3u0z OCA], [http://pdbe.org/3u0z PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3u0z RCSB], [http://www.ebi.ac.uk/pdbsum/3u0z PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3u0z ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/HCN1_MOUSE HCN1_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). Activated by cAMP, and at 10-100 times higher concentrations, also by cGMP. May mediate responses to sour stimuli.<ref>PMID:9630217</ref> <ref>PMID:11675786</ref> | + | [https://www.uniprot.org/uniprot/HCN1_MOUSE HCN1_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). Activated by cAMP, and at 10-100 times higher concentrations, also by cGMP. May mediate responses to sour stimuli.<ref>PMID:9630217</ref> <ref>PMID:11675786</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Ion channels|Ion channels]] | + | *[[Ion channels 3D structures|Ion channels 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Large Structures]] |
| - | [[Category: Arrigoni, C]] | + | [[Category: Mus musculus]] |
| - | [[Category: Bertinetti, D]] | + | [[Category: Arrigoni C]] |
| - | [[Category: Bertrand, J A]] | + | [[Category: Bertinetti D]] |
| - | [[Category: Bolognesi, M]] | + | [[Category: Bertrand JA]] |
| - | [[Category: Fasolini, M]] | + | [[Category: Bolognesi M]] |
| - | [[Category: Gazzarrini, S]] | + | [[Category: Fasolini M]] |
| - | [[Category: Herberg, F W]] | + | [[Category: Gazzarrini S]] |
| - | [[Category: Lolicato, M]] | + | [[Category: Herberg FW]] |
| - | [[Category: Martin, H]] | + | [[Category: Lolicato M]] |
| - | [[Category: Moller, S]] | + | [[Category: Martin H]] |
| - | [[Category: Moroni, A]] | + | [[Category: Moller S]] |
| - | [[Category: Nardini, M]] | + | [[Category: Moroni A]] |
| - | [[Category: Thiel, G]] | + | [[Category: Nardini M]] |
| - | [[Category: Beta sheet]]
| + | [[Category: Thiel G]] |
| - | [[Category: Cnmp binding]]
| + | |
| - | [[Category: Helix]]
| + | |
| - | [[Category: Transport protein]]
| + | |
| Structural highlights
Function
HCN1_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). Activated by cAMP, and at 10-100 times higher concentrations, also by cGMP. May mediate responses to sour stimuli.[1] [2]
Publication Abstract from PubMed
HCN channels are dually activated by hyperpolarization and binding of cAMP to their cyclic nucleotide binding domain (CNBD). HCN isoforms respond differently to cAMP: binding of cAMP shifts activation of HCN2 and HCN4 by 17 mV, but that of HCN1 by only 2-4 mV. To explain the peculiarity of HCN1 we solved the crystal structures and performed a biochemical-biophysical characterization of the C-terminal domain (C linker + CNBD) of the three isoforms. Our main finding is that tetramerization of the C-terminal domain of HCN1 occurs at basal cAMP concentrations while those of HCN2 and HCN4 require cAMP saturating levels. Therefore, HCN1 responds less markedly than HCN2 and HCN4 to cAMP increase because its CNBD is already partly tetrameric. This is confirmed by voltage clamp experiments showing that the right-shifted position of V1/2 in HCN1 is correlated with its propensity to tetramerize in vitro. These data underscore that ligand-induced CNBD tetramerization removes tonic inhibition from the pore of HCN channels.
Tetramerization dynamics of the C-terminal domain underlies isoform-specific cAMP-gating in Hyperpolarization-activated Cyclic Nucleotide gated channels.,Lolicato M, Nardini M, Gazzarrini S, Moeller S, Bertinetti D, Herberg FW, Bolognesi M, Martin H, Fasolini M, Bertrand JA, Arrigoni C, Thiel G, Moroni A J Biol Chem. 2011 Oct 17. PMID:22006928[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Santoro B, Liu DT, Yao H, Bartsch D, Kandel ER, Siegelbaum SA, Tibbs GR. Identification of a gene encoding a hyperpolarization-activated pacemaker channel of brain. Cell. 1998 May 29;93(5):717-29. PMID:9630217
- ↑ Stevens DR, Seifert R, Bufe B, Muller F, Kremmer E, Gauss R, Meyerhof W, Kaupp UB, Lindemann B. Hyperpolarization-activated channels HCN1 and HCN4 mediate responses to sour stimuli. Nature. 2001 Oct 11;413(6856):631-5. PMID:11675786 doi:10.1038/35098087
- ↑ Lolicato M, Nardini M, Gazzarrini S, Moeller S, Bertinetti D, Herberg FW, Bolognesi M, Martin H, Fasolini M, Bertrand JA, Arrigoni C, Thiel G, Moroni A. Tetramerization dynamics of the C-terminal domain underlies isoform-specific cAMP-gating in Hyperpolarization-activated Cyclic Nucleotide gated channels. J Biol Chem. 2011 Oct 17. PMID:22006928 doi:10.1074/jbc.M111.297606
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