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| | ==Solution structure of human J-protein co-chaperone, Dph4== | | ==Solution structure of human J-protein co-chaperone, Dph4== |
| - | <StructureSection load='2l6l' size='340' side='right'caption='[[2l6l]], [[NMR_Ensembles_of_Models | 20 NMR models]]' scene=''> | + | <StructureSection load='2l6l' size='340' side='right'caption='[[2l6l]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2l6l]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2L6L OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2L6L FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2l6l]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2L6L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2L6L FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</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=2l6l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2l6l OCA], [http://pdbe.org/2l6l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2l6l RCSB], [http://www.ebi.ac.uk/pdbsum/2l6l PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2l6l ProSAT]</span></td></tr> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</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=2l6l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2l6l OCA], [https://pdbe.org/2l6l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2l6l RCSB], [https://www.ebi.ac.uk/pdbsum/2l6l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2l6l ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/DJC24_HUMAN DJC24_HUMAN]] Stimulates the ATPase activity of several Hsp70-type chaperones. This ability is enhanced by iron-binding. The iron-bound form is redox-active and can function as electron carrier. Plays a role in the diphthamide biosynthesis, a post-translational modification of histidine which occurs in translation elongation factor 2 (EEF2) which can be ADP-ribosylated by diphtheria toxin and by Pseudomonas exotoxin A (Eta).<ref>PMID:22509046</ref> <ref>PMID:22367199</ref> | + | [https://www.uniprot.org/uniprot/DJC24_HUMAN DJC24_HUMAN] Stimulates the ATPase activity of several Hsp70-type chaperones. This ability is enhanced by iron-binding. The iron-bound form is redox-active and can function as electron carrier. Plays a role in the diphthamide biosynthesis, a post-translational modification of histidine which occurs in translation elongation factor 2 (EEF2) which can be ADP-ribosylated by diphtheria toxin and by Pseudomonas exotoxin A (Eta).<ref>PMID:22509046</ref> <ref>PMID:22367199</ref> |
| - | <div style="background-color:#fffaf0;">
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| - | == Publication Abstract from PubMed ==
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| - | J-proteins are obligate cochaperones of Hsp70s and stimulate their ATPase activity via the J-domain. Although the functions of J-proteins have been well understood in the context of Hsp70s, their additional co-evolved "physiological functions" are still elusive. We report here the solution structure and mechanism of novel iron-mediated functional roles of human Dph4, a type III J-protein playing a vital role in diphthamide biosynthesis and normal development. The NMR structure of Dph4 reveals two domains: a conserved J-domain and a CSL-domain connected via a flexible linker-helix. The linker-helix modulates the conformational flexibility between the two domains, regulating thereby the protein function. Dph4 exhibits a unique ability to bind iron in tetrahedral coordination geometry through cysteines of its CSL-domain. The oxidized Fe-Dph4 shows characteristic UV-visible and electron paramagnetic resonance spectral properties similar to rubredoxins. Iron-bound Dph4 (Fe-Dph4) also undergoes oligomerization, thus potentially functioning as a transient "iron storage protein," thereby regulating the intracellular iron homeostasis. Remarkably, Fe-Dph4 exhibits vital redox and electron carrier activity, which is critical for important metabolic reactions, including diphthamide biosynthesis. Further, we observed that Fe-Dph4 is conformationally better poised to perform Hsp70-dependent functions, thus underlining the significance of iron binding in Dph4. Yeast Jjj3, a functional ortholog of human Dph4 also shows a similar iron-binding property, indicating the conserved nature of iron sequestration across species. Taken together, our findings provide invaluable evidence in favor of additional co-evolved specialized functions of J-proteins, previously not well appreciated.
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| - | Structure and mechanistic insights into novel iron-mediated moonlighting functions of human J-protein cochaperone, Dph4.,Thakur A, Chitoor B, Goswami AV, Pareek G, Atreya HS, D'Silva P J Biol Chem. 2012 Apr 13;287(16):13194-205. Epub 2012 Feb 24. PMID:22367199<ref>PMID:22367199</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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| - | <div class="pdbe-citations 2l6l" style="background-color:#fffaf0;"></div>
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| | ==See Also== | | ==See Also== |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Human]] | + | [[Category: Homo sapiens]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Atreya, H S]] | + | [[Category: Atreya HS]] |
| - | [[Category: Chitoor, B S]] | + | [[Category: Chitoor BS]] |
| - | [[Category: Silva, P D]] | + | [[Category: Silva PD]] |
| - | [[Category: Thakur, A]] | + | [[Category: Thakur A]] |
| - | [[Category: Chaperone]]
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| - | [[Category: Dph4]]
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| - | [[Category: J-domain]]
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| - | [[Category: Zn-csl]]
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