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2l6l

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Revision as of 10:52, 15 February 2023

Solution structure of human J-protein co-chaperone, Dph4

Structural highlights

2l6l is a 1 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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).^[1] ^[2]

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.

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^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Wei H, Xiang L, Wayne AS, Chertov O, FitzGerald DJ, Bera TK, Pastan I. Immunotoxin resistance via reversible methylation of the DPH4 promoter is a unique survival strategy. Proc Natl Acad Sci U S A. 2012 May 1;109(18):6898-903. doi:, 10.1073/pnas.1204523109. Epub 2012 Apr 16. PMID:22509046 doi:http://dx.doi.org/10.1073/pnas.1204523109
↑ Thakur A, Chitoor B, Goswami AV, Pareek G, Atreya HS, D'Silva P. Structure and mechanistic insights into novel iron-mediated moonlighting functions of human J-protein cochaperone, Dph4. J Biol Chem. 2012 Apr 13;287(16):13194-205. Epub 2012 Feb 24. PMID:22367199 doi:http://dx.doi.org/10.1074/jbc.M112.339655
↑ Thakur A, Chitoor B, Goswami AV, Pareek G, Atreya HS, D'Silva P. Structure and mechanistic insights into novel iron-mediated moonlighting functions of human J-protein cochaperone, Dph4. J Biol Chem. 2012 Apr 13;287(16):13194-205. Epub 2012 Feb 24. PMID:22367199 doi:http://dx.doi.org/10.1074/jbc.M112.339655

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2l6l"

@@ Line 1: / Line 1: @@
 ==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 ==
-<table><tr><td colspan='2'>[[2l6l]] is a 1 chain structure with sequence from [https://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 [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>
 <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>
 == 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 ==
@@ Line 25: / Line 25: @@
 __TOC__
 </StructureSection>
-[[Category: Human]]
+[[Category: Homo sapiens]]
 [[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]]
-[[Category: Dph4]]
-[[Category: J-domain]]
-[[Category: Zn-csl]]

2l6l

From Proteopedia

Revision as of 10:52, 15 February 2023

Solution structure of human J-protein co-chaperone, Dph4

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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