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| | ==Drosophila CaMKII-D136N in complex with a phosphorylated fragment of the Eag potassium channel and Mg2+/ADP== | | ==Drosophila CaMKII-D136N in complex with a phosphorylated fragment of the Eag potassium channel and Mg2+/ADP== |
| - | <StructureSection load='5hu3' size='340' side='right' caption='[[5hu3]], [[Resolution|resolution]] 1.89Å' scene=''> | + | <StructureSection load='5hu3' size='340' side='right'caption='[[5hu3]], [[Resolution|resolution]] 1.89Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5hu3]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HU3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5HU3 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5hu3]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Drosophila_melanogaster Drosophila melanogaster]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5HU3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5HU3 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</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]] 1.885Å</td></tr> |
| - | <tr id='NonStdRes'><td class="sblockLbl"><b>[[Non-Standard_Residue|NonStd Res:]]</b></td><td class="sblockDat"><scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ADP:ADENOSINE-5-DIPHOSPHATE'>ADP</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=TPO:PHOSPHOTHREONINE'>TPO</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5fg8|5fg8]], [[5h9b|5h9b]]</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=5hu3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hu3 OCA], [https://pdbe.org/5hu3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5hu3 RCSB], [https://www.ebi.ac.uk/pdbsum/5hu3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5hu3 ProSAT]</span></td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Calcium/calmodulin-dependent_protein_kinase Calcium/calmodulin-dependent protein kinase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=2.7.11.17 2.7.11.17] </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=5hu3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5hu3 OCA], [http://pdbe.org/5hu3 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5hu3 RCSB], [http://www.ebi.ac.uk/pdbsum/5hu3 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5hu3 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/KCC2A_DROME KCC2A_DROME]] A key regulator of plasticity in synaptic physiology and behavior, alterations in its activity produce pleiotrophic effects that involve synaptic transmission and development as well as various aspects of behavior. Directly modulates eag potassium channels.<ref>PMID:11980904</ref> <ref>PMID:14687552</ref> [[http://www.uniprot.org/uniprot/KCNAE_DROME KCNAE_DROME]] Structural component of a potassium channel. Mediates the potassium permeability of membranes; potassium current is regulated by CaMKII and CASK. Has a role in growth of the perineurial glial layer of the larval peripheral nerve.<ref>PMID:11517334</ref> <ref>PMID:11980904</ref> <ref>PMID:15901771</ref> <ref>PMID:1840699</ref> | + | [https://www.uniprot.org/uniprot/KCNAE_DROME KCNAE_DROME] Structural component of a potassium channel. Mediates the potassium permeability of membranes; potassium current is regulated by CaMKII and CASK. Has a role in growth of the perineurial glial layer of the larval peripheral nerve.<ref>PMID:11517334</ref> <ref>PMID:11980904</ref> <ref>PMID:15901771</ref> <ref>PMID:1840699</ref> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | The Drosophila EAG (dEAG) potassium channel is the founding member of the superfamily of KNCH channels, which are involved in cardiac repolarization, neuronal excitability and cellular proliferation. In flies, dEAG is involved in regulation of neuron firing and assembles with CaMKII to form a complex implicated in memory formation. We have characterized the interaction between the kinase domain of CaMKII and a 53-residue fragment of the dEAG channel that includes a canonical CaMKII recognition sequence. Crystal structures together with biochemical/biophysical analysis show a substrate-kinase complex with an unusually tight and extensive interface that appears to be strengthened by phosphorylation of the channel fragment. Electrophysiological recordings show that catalytically active CaMKII is required to observe active dEAG channels. A previously identified phosphorylation site in the recognition sequence is not the substrate for this crucial kinase activity, but rather contributes importantly to the tight interaction of the kinase with the channel. The available data suggest that the dEAG channel is a docking platform for the kinase and that phosphorylation of the channel's kinase recognition sequence modulates the strength of the interaction between the channel and the kinase. |
| | + | |
| | + | The Interaction between the Drosophila EAG Potassium Channel and the Protein Kinase CaMKII Involves an Extensive Interface at the Active Site of the Kinase.,Castro-Rodrigues AF, Zhao Y, Fonseca F, Gabant G, Cadene M, Robertson GA, Morais-Cabral JH J Mol Biol. 2018 Dec 7;430(24):5029-5049. doi: 10.1016/j.jmb.2018.10.015. Epub, 2018 Oct 28. PMID:30381148<ref>PMID:30381148</ref> |
| | + | |
| | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | + | </div> |
| | + | <div class="pdbe-citations 5hu3" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Calcium/calmodulin dependent protein kinase 3D structures|Calcium/calmodulin dependent protein kinase 3D structures]] |
| | + | *[[Potassium channel 3D structures|Potassium channel 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Calcium/calmodulin-dependent protein kinase]] | + | [[Category: Drosophila melanogaster]] |
| - | [[Category: Castro-Rodrigues, A F]] | + | [[Category: Large Structures]] |
| - | [[Category: Morais-Cabral, J H]] | + | [[Category: Castro-Rodrigues AF]] |
| - | [[Category: Complex]] | + | [[Category: Morais-Cabral JH]] |
| - | [[Category: Potassium channel]]
| + | |
| - | [[Category: Protein kinase]]
| + | |
| - | [[Category: Transferase]]
| + | |
| Structural highlights
Function
KCNAE_DROME Structural component of a potassium channel. Mediates the potassium permeability of membranes; potassium current is regulated by CaMKII and CASK. Has a role in growth of the perineurial glial layer of the larval peripheral nerve.[1] [2] [3] [4]
Publication Abstract from PubMed
The Drosophila EAG (dEAG) potassium channel is the founding member of the superfamily of KNCH channels, which are involved in cardiac repolarization, neuronal excitability and cellular proliferation. In flies, dEAG is involved in regulation of neuron firing and assembles with CaMKII to form a complex implicated in memory formation. We have characterized the interaction between the kinase domain of CaMKII and a 53-residue fragment of the dEAG channel that includes a canonical CaMKII recognition sequence. Crystal structures together with biochemical/biophysical analysis show a substrate-kinase complex with an unusually tight and extensive interface that appears to be strengthened by phosphorylation of the channel fragment. Electrophysiological recordings show that catalytically active CaMKII is required to observe active dEAG channels. A previously identified phosphorylation site in the recognition sequence is not the substrate for this crucial kinase activity, but rather contributes importantly to the tight interaction of the kinase with the channel. The available data suggest that the dEAG channel is a docking platform for the kinase and that phosphorylation of the channel's kinase recognition sequence modulates the strength of the interaction between the channel and the kinase.
The Interaction between the Drosophila EAG Potassium Channel and the Protein Kinase CaMKII Involves an Extensive Interface at the Active Site of the Kinase.,Castro-Rodrigues AF, Zhao Y, Fonseca F, Gabant G, Cadene M, Robertson GA, Morais-Cabral JH J Mol Biol. 2018 Dec 7;430(24):5029-5049. doi: 10.1016/j.jmb.2018.10.015. Epub, 2018 Oct 28. PMID:30381148[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Yager J, Richards S, Hekmat-Scafe DS, Hurd DD, Sundaresan V, Caprette DR, Saxton WM, Carlson JR, Stern M. Control of Drosophila perineurial glial growth by interacting neurotransmitter-mediated signaling pathways. Proc Natl Acad Sci U S A. 2001 Aug 28;98(18):10445-50. Epub 2001 Aug 21. PMID:11517334 doi:http://dx.doi.org/10.1073/pnas.191107698
- ↑ Wang Z, Wilson GF, Griffith LC. Calcium/calmodulin-dependent protein kinase II phosphorylates and regulates the Drosophila eag potassium channel. J Biol Chem. 2002 Jul 5;277(27):24022-9. Epub 2002 Apr 29. PMID:11980904 doi:http://dx.doi.org/10.1074/jbc.M201949200
- ↑ Marble DD, Hegle AP, Snyder ED 2nd, Dimitratos S, Bryant PJ, Wilson GF. Camguk/CASK enhances Ether-a-go-go potassium current by a phosphorylation-dependent mechanism. J Neurosci. 2005 May 18;25(20):4898-907. PMID:15901771 doi:http://dx.doi.org/10.1523/JNEUROSCI.4566-04.2005
- ↑ Warmke J, Drysdale R, Ganetzky B. A distinct potassium channel polypeptide encoded by the Drosophila eag locus. Science. 1991 Jun 14;252(5012):1560-2. PMID:1840699
- ↑ Castro-Rodrigues AF, Zhao Y, Fonseca F, Gabant G, Cadene M, Robertson GA, Morais-Cabral JH. The Interaction between the Drosophila EAG Potassium Channel and the Protein Kinase CaMKII Involves an Extensive Interface at the Active Site of the Kinase. J Mol Biol. 2018 Dec 7;430(24):5029-5049. doi: 10.1016/j.jmb.2018.10.015. Epub, 2018 Oct 28. PMID:30381148 doi:http://dx.doi.org/10.1016/j.jmb.2018.10.015
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