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| | ==Crystal structure of Drosophila melanogaster DJ-1beta== | | ==Crystal structure of Drosophila melanogaster DJ-1beta== |
| - | <StructureSection load='4e08' size='340' side='right' caption='[[4e08]], [[Resolution|resolution]] 2.00Å' scene=''> | + | <StructureSection load='4e08' size='340' side='right'caption='[[4e08]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4e08]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Drome Drome]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4E08 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4E08 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4e08]] 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=4E08 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4E08 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CG1349, dj-1 beta, dj-1-beta, dj-1beta, Dmel_CG1349 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=7227 DROME])</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=4e08 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e08 OCA], [https://pdbe.org/4e08 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4e08 RCSB], [https://www.ebi.ac.uk/pdbsum/4e08 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4e08 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=4e08 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4e08 OCA], [http://pdbe.org/4e08 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4e08 RCSB], [http://www.ebi.ac.uk/pdbsum/4e08 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4e08 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | + | == Function == |
| | + | [[https://www.uniprot.org/uniprot/DJ1B_DROME DJ1B_DROME]] Plays an important role in cell protection against oxidative stress and cell death by acting as a oxidative stress sensor (PubMed:16139214, PubMed:16203113, PubMed:16894167, PubMed:20457924). Does not play a role in methylglyoxal detoxification (PubMed:27903648). Plays a role in mitochondrial function together with Pink1 (PubMed:20457924). In motor neurons regulates structural synaptic plasticity of locomotor behavior as part of the PTEN-phosphatidylinositol 3-kinase pathway in response to oxygen species (ROS) levels (PubMed:30540251).<ref>PMID:16139214</ref> <ref>PMID:16203113</ref> <ref>PMID:16894167</ref> <ref>PMID:20457924</ref> <ref>PMID:27903648</ref> <ref>PMID:30540251</ref> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </div> | | </div> |
| | <div class="pdbe-citations 4e08" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 4e08" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Protein DJ-1|Protein DJ-1]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Drome]] | + | [[Category: Drosophila melanogaster]] |
| - | [[Category: Lin, J]] | + | [[Category: Large Structures]] |
| - | [[Category: Prahlad, J]] | + | [[Category: Lin J]] |
| - | [[Category: Wilson, M A]] | + | [[Category: Prahlad J]] |
| - | [[Category: Flavodoxin-like fold]] | + | [[Category: Wilson MA]] |
| - | [[Category: Motor protein]]
| + | |
| - | [[Category: Stress response]]
| + | |
| Structural highlights
Function
[DJ1B_DROME] Plays an important role in cell protection against oxidative stress and cell death by acting as a oxidative stress sensor (PubMed:16139214, PubMed:16203113, PubMed:16894167, PubMed:20457924). Does not play a role in methylglyoxal detoxification (PubMed:27903648). Plays a role in mitochondrial function together with Pink1 (PubMed:20457924). In motor neurons regulates structural synaptic plasticity of locomotor behavior as part of the PTEN-phosphatidylinositol 3-kinase pathway in response to oxygen species (ROS) levels (PubMed:30540251).[1] [2] [3] [4] [5] [6]
Publication Abstract from PubMed
DJ-1 is a conserved, disease-associated protein that protects against oxidative stress and mitochondrial damage in multiple organisms. Human DJ-1 contains a functionally essential cysteine residue (Cys106) whose oxidation is important for regulating protein function by an unknown mechanism. This residue is well-conserved in other DJ-1 homologues, including two (DJ-1alpha and DJ-1beta) in Drosophila melanogaster. Because D. melanogaster is a powerful model system for studying DJ-1 function, we have determined the crystal structure and impact of cysteine oxidation on Drosophila DJ-1beta. The structure of D. melanogaster DJ-1beta is similar to that of human DJ-1, although two important residues in the human protein, Met26 and His126, are not conserved in DJ-1beta. His126 in human DJ-1 is substituted with a tyrosine in DJ-1beta, and this residue is not able to compose a putative catalytic dyad with Cys106 that was proposed to be important in the human protein. The reactive cysteine in DJ-1 is oxidized readily to the cysteine-sulfinic acid in both flies and humans, and this may regulate the cytoprotective function of the protein. We show that the oxidation of this conserved cysteine residue to its sulfinate form (Cys-SO(2)(-)) results in considerable thermal stabilization of both Drosophila DJ-1beta and human DJ-1. Therefore, protein stabilization is one potential mechanism by which cysteine oxidation may regulate DJ-1 function in vivo. More generally, most close DJ-1 homologues are likely stabilized by cysteine-sulfinic acid formation but destabilized by further oxidation, suggesting that they are biphasically regulated by oxidative modification.
Conservation of Oxidative Protein Stabilization in an Insect Homologue of Parkinsonism-Associated Protein DJ-1.,Lin J, Prahlad J, Wilson MA Biochemistry. 2012 Apr 24. PMID:22515803[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Menzies FM, Yenisetti SC, Min KT. Roles of Drosophila DJ-1 in survival of dopaminergic neurons and oxidative stress. Curr Biol. 2005 Sep 6;15(17):1578-82. doi: 10.1016/j.cub.2005.07.036. PMID:16139214 doi:http://dx.doi.org/10.1016/j.cub.2005.07.036
- ↑ Park J, Kim SY, Cha GH, Lee SB, Kim S, Chung J. Drosophila DJ-1 mutants show oxidative stress-sensitive locomotive dysfunction. Gene. 2005 Nov 21;361:133-9. doi: 10.1016/j.gene.2005.06.040. Epub 2005 Oct 3. PMID:16203113 doi:http://dx.doi.org/10.1016/j.gene.2005.06.040
- ↑ Meulener MC, Xu K, Thomson L, Ischiropoulos H, Bonini NM. Mutational analysis of DJ-1 in Drosophila implicates functional inactivation by oxidative damage and aging. Proc Natl Acad Sci U S A. 2006 Aug 15;103(33):12517-22. doi:, 10.1073/pnas.0601891103. Epub 2006 Aug 7. PMID:16894167 doi:http://dx.doi.org/10.1073/pnas.0601891103
- ↑ Hao LY, Giasson BI, Bonini NM. DJ-1 is critical for mitochondrial function and rescues PINK1 loss of function. Proc Natl Acad Sci U S A. 2010 May 25;107(21):9747-52. doi:, 10.1073/pnas.0911175107. Epub 2010 May 10. PMID:20457924 doi:http://dx.doi.org/10.1073/pnas.0911175107
- ↑ Pfaff DH, Fleming T, Nawroth P, Teleman AA. Evidence Against a Role for the Parkinsonism-associated Protein DJ-1 in Methylglyoxal Detoxification. J Biol Chem. 2017 Jan 13;292(2):685-690. doi: 10.1074/jbc.M116.743823. Epub 2016 , Nov 30. PMID:27903648 doi:http://dx.doi.org/10.1074/jbc.M116.743823
- ↑ Oswald MC, Brooks PS, Zwart MF, Mukherjee A, West RJ, Giachello CN, Morarach K, Baines RA, Sweeney ST, Landgraf M. Reactive oxygen species regulate activity-dependent neuronal plasticity in Drosophila. Elife. 2018 Dec 17;7. pii: 39393. doi: 10.7554/eLife.39393. PMID:30540251 doi:http://dx.doi.org/10.7554/eLife.39393
- ↑ Lin J, Prahlad J, Wilson MA. Conservation of Oxidative Protein Stabilization in an Insect Homologue of Parkinsonism-Associated Protein DJ-1. Biochemistry. 2012 Apr 24. PMID:22515803 doi:10.1021/bi3003296
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