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| | <StructureSection load='5mpm' size='340' side='right'caption='[[5mpm]], [[Resolution|resolution]] 3.30Å' scene=''> | | <StructureSection load='5mpm' size='340' side='right'caption='[[5mpm]], [[Resolution|resolution]] 3.30Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[5mpm]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MPM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5MPM FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[5mpm]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Sus_scrofa Sus scrofa]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MPM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5MPM FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CZA:(6AR,11AS,11BR)-10-ACETYL-9-HYDROXY-7,7-DIMETHYL-2,6,6A,7,11A,11B-HEXAHYDRO-11H-PYRROLO[1,2 2,3]ISOINDOLO[4,5,6-CD]INDOL-11-ONE'>CZA</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MGF:TRIFLUOROMAGNESATE'>MGF</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]] 3.3Å</td></tr> |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[http://en.wikipedia.org/wiki/Calcium-transporting_ATPase Calcium-transporting ATPase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.6.3.8 3.6.3.8] </span></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CZA:(6AR,11AS,11BR)-10-ACETYL-9-HYDROXY-7,7-DIMETHYL-2,6,6A,7,11A,11B-HEXAHYDRO-11H-PYRROLO[1,2 2,3]ISOINDOLO[4,5,6-CD]INDOL-11-ONE'>CZA</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=MGF:TRIFLUOROMAGNESATE'>MGF</scene></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=5mpm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mpm OCA], [http://pdbe.org/5mpm PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mpm RCSB], [http://www.ebi.ac.uk/pdbsum/5mpm PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mpm 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=5mpm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mpm OCA], [https://pdbe.org/5mpm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5mpm RCSB], [https://www.ebi.ac.uk/pdbsum/5mpm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5mpm ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/AT2A2_PIG AT2A2_PIG]] This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen. Isoform SERCA2A is involved in the regulation of the contraction/relaxation cycle. Acts as a regulator of TNFSF11-mediated Ca(2+) signaling pathways via its interaction with TMEM64 which is critical for the TNFSF11-induced CREB1 activation and mitochondrial ROS generation necessary for proper osteoclast generation. Association between TMEM64 and SERCA2 in the ER leads to cytosolic Ca (2+) spiking for activation of NFATC1 and production of mitochondrial ROS, thereby triggering Ca (2+) signaling cascades that promote osteoclast differentiation and activation.[UniProtKB:O55143] | + | [https://www.uniprot.org/uniprot/AT2A2_PIG AT2A2_PIG] This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen. Isoform SERCA2A is involved in the regulation of the contraction/relaxation cycle. Acts as a regulator of TNFSF11-mediated Ca(2+) signaling pathways via its interaction with TMEM64 which is critical for the TNFSF11-induced CREB1 activation and mitochondrial ROS generation necessary for proper osteoclast generation. Association between TMEM64 and SERCA2 in the ER leads to cytosolic Ca (2+) spiking for activation of NFATC1 and production of mitochondrial ROS, thereby triggering Ca (2+) signaling cascades that promote osteoclast differentiation and activation.[UniProtKB:O55143] |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Calcium-transporting ATPase]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| | [[Category: Sus scrofa]] | | [[Category: Sus scrofa]] |
| - | [[Category: Andersen, J L]] | + | [[Category: Andersen JL]] |
| - | [[Category: Drachmann, N D]] | + | [[Category: Drachmann ND]] |
| - | [[Category: Nissen, P]] | + | [[Category: Nissen P]] |
| - | [[Category: Olesen, C]] | + | [[Category: Olesen C]] |
| - | [[Category: Sitsel, A]] | + | [[Category: Sitsel A]] |
| - | [[Category: Ca2+-atpase]]
| + | |
| - | [[Category: Hydrolase]]
| + | |
| - | [[Category: Serca]]
| + | |
| Structural highlights
Function
AT2A2_PIG This magnesium-dependent enzyme catalyzes the hydrolysis of ATP coupled with the translocation of calcium from the cytosol to the sarcoplasmic reticulum lumen. Isoform SERCA2A is involved in the regulation of the contraction/relaxation cycle. Acts as a regulator of TNFSF11-mediated Ca(2+) signaling pathways via its interaction with TMEM64 which is critical for the TNFSF11-induced CREB1 activation and mitochondrial ROS generation necessary for proper osteoclast generation. Association between TMEM64 and SERCA2 in the ER leads to cytosolic Ca (2+) spiking for activation of NFATC1 and production of mitochondrial ROS, thereby triggering Ca (2+) signaling cascades that promote osteoclast differentiation and activation.[UniProtKB:O55143]
Publication Abstract from PubMed
The sarcoplasmic/endoplasmic reticulum Ca(2+)-ATPase 2a (SERCA2a) performs active reuptake of cytoplasmic Ca(2+) and is a major regulator of cardiac muscle contractility. Dysfunction or dysregulation of SERCA2a is associated with heart failure, while restoring its function is considered as a therapeutic strategy to restore cardiac performance. However, its structure has not yet been determined. Based on native, active protein purified from pig ventricular muscle, we present the first crystal structures of SERCA2a, determined in the CPA-stabilized E2-AlF4- form (3.3 A) and the Ca(2+)-occluded [Ca2]E1-AMPPCP form (4.0 A). The structures are similar to the skeletal muscle isoform SERCA1a pointing to a conserved mechanism. We seek to explain the kinetic differences between SERCA1a and SERCA2a. We find that several isoform-specific residues are acceptor sites for post-translational modifications. In addition, molecular dynamics simulations predict that isoform-specific residues support distinct intramolecular interactions in SERCA2a and SERCA1a. Our experimental observations further indicate that isoform-specific intramolecular interactions are functionally relevant, and may explain the kinetic differences between SERCA2a and SERCA1a.
Structures of the heart specific SERCA2a Ca(2+)-ATPase.,Sitsel A, De Raeymaecker J, Drachmann ND, Derua R, Smaardijk S, Andersen JL, Vandecaetsbeek I, Chen J, De Maeyer M, Waelkens E, Olesen C, Vangheluwe P, Nissen P EMBO J. 2019 Feb 18. pii: embj.2018100020. doi: 10.15252/embj.2018100020. PMID:30777856[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Sitsel A, De Raeymaecker J, Drachmann ND, Derua R, Smaardijk S, Andersen JL, Vandecaetsbeek I, Chen J, De Maeyer M, Waelkens E, Olesen C, Vangheluwe P, Nissen P. Structures of the heart specific SERCA2a Ca(2+)-ATPase. EMBO J. 2019 Feb 18. pii: embj.2018100020. doi: 10.15252/embj.2018100020. PMID:30777856 doi:http://dx.doi.org/10.15252/embj.2018100020
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