2l6l
From Proteopedia
(Difference between revisions)
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== Structural highlights == | == Structural highlights == | ||
<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> | <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" id="ligandDat"><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='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> | <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 == | ||
[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> | [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;"> | ||
| - | == Publication Abstract from PubMed == | ||
| - | 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> | ||
| - | </div> | ||
| - | <div class="pdbe-citations 2l6l" style="background-color:#fffaf0;"></div> | ||
==See Also== | ==See Also== | ||
Current revision
Solution structure of human J-protein co-chaperone, Dph4
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