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| | ==Crystal structure of trimeric frataxin from the yeast Saccharomyces cerevisiae== | | ==Crystal structure of trimeric frataxin from the yeast Saccharomyces cerevisiae== |
| - | <StructureSection load='2fql' size='340' side='right' caption='[[2fql]], [[Resolution|resolution]] 3.01Å' scene=''> | + | <StructureSection load='2fql' size='340' side='right'caption='[[2fql]], [[Resolution|resolution]] 3.01Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2fql]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Atcc_18824 Atcc 18824]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FQL OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2FQL FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2fql]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2FQL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2FQL FirstGlance]. <br> |
| - | </td></tr><tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">YFH1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=4932 ATCC 18824])</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]] 3.01Å</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=2fql FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fql OCA], [http://pdbe.org/2fql PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2fql RCSB], [http://www.ebi.ac.uk/pdbsum/2fql PDBsum]</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=2fql FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2fql OCA], [https://pdbe.org/2fql PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2fql RCSB], [https://www.ebi.ac.uk/pdbsum/2fql PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2fql ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/FRDA_YEAST FRDA_YEAST]] Promotes the biosynthesis of heme as well as the assembly and repair of iron-sulfur clusters by delivering Fe(2+) to proteins involved in these pathways. Plays a role in the protection against iron-catalyzed oxidative stress through its ability to catalyze the oxidation of Fe(2+) to Fe(3+). Can store large amounts of the metal in the form of a ferrihydrite mineral by oligomerization. May be involved in regulation of the mitochondrial electron transport chain.<ref>PMID:9180083</ref> <ref>PMID:9988680</ref> <ref>PMID:15961414</ref> <ref>PMID:16371422</ref> <ref>PMID:19884169</ref> <ref>PMID:17027502</ref> | + | [https://www.uniprot.org/uniprot/FRDA_YEAST FRDA_YEAST] Promotes the biosynthesis of heme as well as the assembly and repair of iron-sulfur clusters by delivering Fe(2+) to proteins involved in these pathways. Plays a role in the protection against iron-catalyzed oxidative stress through its ability to catalyze the oxidation of Fe(2+) to Fe(3+). Can store large amounts of the metal in the form of a ferrihydrite mineral by oligomerization. May be involved in regulation of the mitochondrial electron transport chain.<ref>PMID:9180083</ref> <ref>PMID:9988680</ref> <ref>PMID:15961414</ref> <ref>PMID:16371422</ref> <ref>PMID:19884169</ref> <ref>PMID:17027502</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
| | Check<jmol> | | Check<jmol> |
| | <jmolCheckbox> | | <jmolCheckbox> |
| - | <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fq/2fql_consurf.spt"</scriptWhenChecked> | + | <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fq/2fql_consurf.spt"</scriptWhenChecked> |
| | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> | | <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked> |
| | <text>to colour the structure by Evolutionary Conservation</text> | | <text>to colour the structure by Evolutionary Conservation</text> |
| | </jmolCheckbox> | | </jmolCheckbox> |
| - | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/chain_selection.php?pdb_ID=2ata ConSurf]. | + | </jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2fql ConSurf]. |
| | <div style="clear:both"></div> | | <div style="clear:both"></div> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
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| | </div> | | </div> |
| | <div class="pdbe-citations 2fql" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 2fql" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Frataxin|Frataxin]] |
| | + | *[[Frataxin 3D Structures|Frataxin 3D Structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: Atcc 18824]] | + | [[Category: Large Structures]] |
| - | [[Category: Al-Karadaghi, S]] | + | [[Category: Saccharomyces cerevisiae]] |
| - | [[Category: Karlberg, T]] | + | [[Category: Al-Karadaghi S]] |
| - | [[Category: Alpha/beta sandwich]]
| + | [[Category: Karlberg T]] |
| - | [[Category: Iron-storage]]
| + | |
| - | [[Category: Metallochaperone]] | + | |
| - | [[Category: Transport protein]]
| + | |
| Structural highlights
Function
FRDA_YEAST Promotes the biosynthesis of heme as well as the assembly and repair of iron-sulfur clusters by delivering Fe(2+) to proteins involved in these pathways. Plays a role in the protection against iron-catalyzed oxidative stress through its ability to catalyze the oxidation of Fe(2+) to Fe(3+). Can store large amounts of the metal in the form of a ferrihydrite mineral by oligomerization. May be involved in regulation of the mitochondrial electron transport chain.[1] [2] [3] [4] [5] [6]
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Defects in the mitochondrial protein frataxin are responsible for Friedreich ataxia, a neurodegenerative and cardiac disease that affects 1:40,000 children. Here, we present the crystal structures of the iron-free and iron-loaded frataxin trimers, and a single-particle electron microscopy reconstruction of a 24 subunit oligomer. The structures reveal fundamental aspects of the frataxin mechanism. The trimer has a central channel in which one atom of iron binds. Two conformations of the channel with different metal-binding affinities suggest that a gating mechanism controls whether the bound iron is delivered to other proteins or transferred to detoxification sites. The trimer constitutes the basic structural unit of the 24 subunit oligomer. The architecture of this oligomer and several features of the trimer structure demonstrate striking similarities to the iron-storage protein ferritin. The data reveal how stepwise assembly provides frataxin with the structural flexibility to perform two functions: metal delivery and detoxification.
The structures of frataxin oligomers reveal the mechanism for the delivery and detoxification of iron.,Karlberg T, Schagerlof U, Gakh O, Park S, Ryde U, Lindahl M, Leath K, Garman E, Isaya G, Al-Karadaghi S Structure. 2006 Oct;14(10):1535-46. PMID:17027502[7]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Babcock M, de Silva D, Oaks R, Davis-Kaplan S, Jiralerspong S, Montermini L, Pandolfo M, Kaplan J. Regulation of mitochondrial iron accumulation by Yfh1p, a putative homolog of frataxin. Science. 1997 Jun 13;276(5319):1709-12. PMID:9180083
- ↑ Radisky DC, Babcock MC, Kaplan J. The yeast frataxin homologue mediates mitochondrial iron efflux. Evidence for a mitochondrial iron cycle. J Biol Chem. 1999 Feb 19;274(8):4497-9. PMID:9988680
- ↑ Gonzalez-Cabo P, Vazquez-Manrique RP, Garcia-Gimeno MA, Sanz P, Palau F. Frataxin interacts functionally with mitochondrial electron transport chain proteins. Hum Mol Genet. 2005 Aug 1;14(15):2091-8. Epub 2005 Jun 16. PMID:15961414 doi:10.1093/hmg/ddi214
- ↑ Gakh O, Park S, Liu G, Macomber L, Imlay JA, Ferreira GC, Isaya G. Mitochondrial iron detoxification is a primary function of frataxin that limits oxidative damage and preserves cell longevity. Hum Mol Genet. 2006 Feb 1;15(3):467-79. Epub 2005 Dec 21. PMID:16371422 doi:10.1093/hmg/ddi461
- ↑ Leidgens S, De Smet S, Foury F. Frataxin interacts with Isu1 through a conserved tryptophan in its beta-sheet. Hum Mol Genet. 2010 Jan 15;19(2):276-86. Epub 2009 Nov 2. PMID:19884169 doi:ddp495
- ↑ Karlberg T, Schagerlof U, Gakh O, Park S, Ryde U, Lindahl M, Leath K, Garman E, Isaya G, Al-Karadaghi S. The structures of frataxin oligomers reveal the mechanism for the delivery and detoxification of iron. Structure. 2006 Oct;14(10):1535-46. PMID:17027502 doi:10.1016/j.str.2006.08.010
- ↑ Karlberg T, Schagerlof U, Gakh O, Park S, Ryde U, Lindahl M, Leath K, Garman E, Isaya G, Al-Karadaghi S. The structures of frataxin oligomers reveal the mechanism for the delivery and detoxification of iron. Structure. 2006 Oct;14(10):1535-46. PMID:17027502 doi:10.1016/j.str.2006.08.010
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