4djc
From Proteopedia
(Difference between revisions)
(New page: '''Unreleased structure''' The entry 4djc is ON HOLD Authors: Sarhan, M.F., Tung, C-C., Van Petegem, F, Ahern, C.A. Description: 1.35 A crystal structure of the NaV1.5 DIII-IV-Ca/CaM c...) |
|||
| (10 intermediate revisions not shown.) | |||
| Line 1: | Line 1: | ||
| - | '''Unreleased structure''' | ||
| - | The entry | + | ==1.35 A crystal structure of the NaV1.5 DIII-IV-Ca/CaM complex== |
| + | <StructureSection load='4djc' size='340' side='right'caption='[[4djc]], [[Resolution|resolution]] 1.35Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[4djc]] is a 2 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=4DJC OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4DJC FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=IPA:ISOPROPYL+ALCOHOL'>IPA</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=4djc FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4djc OCA], [https://pdbe.org/4djc PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4djc RCSB], [https://www.ebi.ac.uk/pdbsum/4djc PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4djc ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Disease == | ||
| + | [[https://www.uniprot.org/uniprot/CALM1_HUMAN CALM1_HUMAN]] The disease is caused by mutations affecting the gene represented in this entry. Mutations in CALM1 are the cause of CPVT4. The disease is caused by mutations affecting the gene represented in this entry. Mutations in CALM1 are the cause of LQT14. | ||
| + | == Function == | ||
| + | [[https://www.uniprot.org/uniprot/CALM1_HUMAN CALM1_HUMAN]] Calmodulin mediates the control of a large number of enzymes, ion channels, aquaporins and other proteins through calcium-binding. Among the enzymes to be stimulated by the calmodulin-calcium complex are a number of protein kinases and phosphatases. Together with CCP110 and centrin, is involved in a genetic pathway that regulates the centrosome cycle and progression through cytokinesis (PubMed:16760425). Mediates calcium-dependent inactivation of CACNA1C (PubMed:26969752). Positively regulates calcium-activated potassium channel activity of KCNN2 (PubMed:27165696).<ref>PMID:16760425</ref> <ref>PMID:23893133</ref> <ref>PMID:26969752</ref> <ref>PMID:27165696</ref> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Voltage-gated sodium channels underlie the rapid regenerative upstroke of action potentials and are modulated by cytoplasmic calcium ions through a poorly understood mechanism. We describe the 1.35 A crystal structure of Ca(2+)-bound calmodulin (Ca(2+)/CaM) in complex with the inactivation gate (DIII-IV linker) of the cardiac sodium channel (Na(V)1.5). The complex harbors the positions of five disease mutations involved with long Q-T type 3 and Brugada syndromes. In conjunction with isothermal titration calorimetry, we identify unique inactivation-gate mutations that enhance or diminish Ca(2+)/CaM binding, which, in turn, sensitize or abolish Ca(2+) regulation of full-length channels in electrophysiological experiments. Additional biochemical experiments support a model whereby a single Ca(2+)/CaM bridges the C-terminal IQ motif to the DIII-IV linker via individual N and C lobes, respectively. The data suggest that Ca(2+)/CaM destabilizes binding of the inactivation gate to its receptor, thus biasing inactivation toward more depolarized potentials. | ||
| - | + | Crystallographic basis for calcium regulation of sodium channels.,Sarhan MF, Tung CC, Van Petegem F, Ahern CA Proc Natl Acad Sci U S A. 2012 Feb 28;109(9):3558-63. Epub 2012 Feb 13. PMID:22331908<ref>PMID:22331908</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| + | </div> | ||
| + | <div class="pdbe-citations 4djc" style="background-color:#fffaf0;"></div> | ||
| + | |||
| + | ==See Also== | ||
| + | *[[Calmodulin 3D structures|Calmodulin 3D structures]] | ||
| + | *[[Ion channels 3D structures|Ion channels 3D structures]] | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Homo sapiens]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Ahern CA]] | ||
| + | [[Category: Sarhan MF]] | ||
| + | [[Category: Tung C-C]] | ||
| + | [[Category: Van Petegem F]] | ||
Current revision
1.35 A crystal structure of the NaV1.5 DIII-IV-Ca/CaM complex
| |||||||||||
