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| | ==Trip8b-1a#206-567 interacting with the carboxy-terminal seven residues of HCN2== | | ==Trip8b-1a#206-567 interacting with the carboxy-terminal seven residues of HCN2== |
| - | <StructureSection load='4eqf' size='340' side='right' caption='[[4eqf]], [[Resolution|resolution]] 3.00Å' scene=''> | + | <StructureSection load='4eqf' size='340' side='right'caption='[[4eqf]], [[Resolution|resolution]] 3.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4eqf]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4EQF OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4EQF FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4eqf]] 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=4EQF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4EQF FirstGlance]. <br> |
| - | </td></tr><tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1fch|1fch]], [[3cvp|3cvp]], [[3cvq|3cvq]]</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]] 3Å</td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Pex5l, Pex2, Pex5r, Pxr2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus])</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=4eqf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eqf OCA], [https://pdbe.org/4eqf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4eqf RCSB], [https://www.ebi.ac.uk/pdbsum/4eqf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4eqf 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=4eqf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4eqf OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4eqf RCSB], [http://www.ebi.ac.uk/pdbsum/4eqf PDBsum]</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/PEX5R_MOUSE PEX5R_MOUSE] Accessory subunit of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, regulating their cell-surface expression and cyclic nucleotide dependence.<ref>PMID:22550182</ref> |
| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | Ion channels operate in intact tissues as part of large macromolecular complexes that can include cytoskeletal proteins, scaffolding proteins, signaling molecules, and a litany of other molecules. The proteins that make up these complexes can influence the trafficking, localization, and biophysical properties of the channel. TRIP8b (tetratricopetide repeat-containing Rab8b-interacting protein) is a recently discovered accessory subunit of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels that contributes to the substantial dendritic localization of HCN channels in many types of neurons. TRIP8b interacts with the carboxyl-terminal region of HCN channels and regulates their cell-surface expression level and cyclic nucleotide dependence. Here we examine the molecular determinants of TRIP8b binding to HCN2 channels. Using a single-molecule fluorescence bleaching method, we found that TRIP8b and HCN2 form an obligate 4:4 complex in intact channels. Fluorescence-detection size-exclusion chromatography and fluorescence anisotropy allowed us to confirm that two different domains in the carboxyl-terminal portion of TRIP8b-the tetratricopepide repeat region and the TRIP8b conserved region-interact with two different regions of the HCN carboxyl-terminal region: the carboxyl-terminal three amino acids (SNL) and the cyclic nucleotide-binding domain, respectively. And finally, using X-ray crystallography, we determined the atomic structure of the tetratricopepide region of TRIP8b in complex with a peptide of the carboxy-terminus of HCN2. Together, these experiments begin to uncover the mechanism for TRIP8b binding and regulation of HCN channels.
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| - | Structure and stoichiometry of an accessory subunit TRIP8b interaction with hyperpolarization-activated cyclic nucleotide-gated channels.,Bankston JR, Camp SS, Dimaio F, Lewis AS, Chetkovich DM, Zagotta WN Proc Natl Acad Sci U S A. 2012 May 15;109(20):7899-904. Epub 2012 May 1. PMID:22550182<ref>PMID:22550182</ref>
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| - | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
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| - | </div>
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| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Large Structures]] |
| | [[Category: Mus musculus]] | | [[Category: Mus musculus]] |
| - | [[Category: Bankston, J R]] | + | [[Category: Bankston JR]] |
| - | [[Category: Camp, S S]] | + | [[Category: Camp SS]] |
| - | [[Category: Chetkovich, D M]] | + | [[Category: Chetkovich DM]] |
| - | [[Category: Dimaio, F]] | + | [[Category: Dimaio F]] |
| - | [[Category: Lewis, A S]] | + | [[Category: Lewis AS]] |
| - | [[Category: Zagotta, W N]] | + | [[Category: Zagotta WN]] |
| - | [[Category: Accessory protein]]
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| - | [[Category: Accessory protein for hcn channel]]
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| - | [[Category: Hcn]]
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| - | [[Category: Protein binding-transport protein complex]]
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| - | [[Category: Tetratricopeptide repeat]]
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| - | [[Category: Tpr]]
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