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| | ==Solution structure human HCN2 CNBD in the cAMP-unbound state== | | ==Solution structure human HCN2 CNBD in the cAMP-unbound state== |
| - | <StructureSection load='2mpf' size='340' side='right' caption='[[2mpf]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2mpf' size='340' side='right'caption='[[2mpf]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2mpf]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MPF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2MPF FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2mpf]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2MPF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2MPF FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">HCN2, BCNG2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=2mpf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mpf OCA], [http://pdbe.org/2mpf PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2mpf RCSB], [http://www.ebi.ac.uk/pdbsum/2mpf PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2mpf 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=2mpf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2mpf OCA], [https://pdbe.org/2mpf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2mpf RCSB], [https://www.ebi.ac.uk/pdbsum/2mpf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2mpf ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/HCN2_HUMAN HCN2_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). 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 (By similarity). | + | [https://www.uniprot.org/uniprot/HCN2_HUMAN HCN2_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). 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 (By similarity). |
| | <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: Human]] | + | [[Category: Homo sapiens]] |
| - | [[Category: Banci, L]] | + | [[Category: Large Structures]] |
| - | [[Category: Cantini, F]] | + | [[Category: Banci L]] |
| - | [[Category: Hammann, C]] | + | [[Category: Cantini F]] |
| - | [[Category: Matzapetakis, M]] | + | [[Category: Hammann C]] |
| - | [[Category: Moroni, A]] | + | [[Category: Matzapetakis M]] |
| - | [[Category: Pauleta, S R]] | + | [[Category: Moroni A]] |
| - | [[Category: Santoro, B]] | + | [[Category: Pauleta SR]] |
| - | [[Category: Saponaro, A]] | + | [[Category: Santoro B]] |
| - | [[Category: Thiel, G]] | + | [[Category: Saponaro A]] |
| - | [[Category: Hcn channel]]
| + | [[Category: Thiel G]] |
| - | [[Category: Transport protein]]
| + | |
| Structural highlights
Function
HCN2_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). 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 (By similarity).
Publication Abstract from PubMed
cAMP signaling in the brain mediates several higher order neural processes. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels directly bind cAMP through their cytoplasmic cyclic nucleotide binding domain (CNBD), thus playing a unique role in brain function. Neuronal HCN channels are also regulated by tetratricopeptide repeat-containing Rab8b interacting protein (TRIP8b), an auxiliary subunit that antagonizes the effects of cAMP by interacting with the channel CNBD. To unravel the molecular mechanisms underlying the dual regulation of HCN channel activity by cAMP/TRIP8b, we determined the NMR solution structure of the HCN2 channel CNBD in the cAMP-free form and mapped on it the TRIP8b interaction site. We reconstruct here the full conformational changes induced by cAMP binding to the HCN channel CNBD. Our results show that TRIP8b does not compete with cAMP for the same binding region; rather, it exerts its inhibitory action through an allosteric mechanism, preventing the cAMP-induced conformational changes in the HCN channel CNBD.
Structural basis for the mutual antagonism of cAMP and TRIP8b in regulating HCN channel function.,Saponaro A, Pauleta SR, Cantini F, Matzapetakis M, Hammann C, Donadoni C, Hu L, Thiel G, Banci L, Santoro B, Moroni A Proc Natl Acad Sci U S A. 2014 Sep 2. pii: 201410389. PMID:25197093[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Saponaro A, Pauleta SR, Cantini F, Matzapetakis M, Hammann C, Donadoni C, Hu L, Thiel G, Banci L, Santoro B, Moroni A. Structural basis for the mutual antagonism of cAMP and TRIP8b in regulating HCN channel function. Proc Natl Acad Sci U S A. 2014 Sep 2. pii: 201410389. PMID:25197093 doi:http://dx.doi.org/10.1073/pnas.1410389111
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