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| - | [[Image:3oer.png|left|200px]] | |
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| - | <!-- | + | ==Crystal structure of trimeric frataxin from the yeast saccharomyces cerevisiae, complexed with cobalt== |
| - | The line below this paragraph, containing "STRUCTURE_3oer", creates the "Structure Box" on the page.
| + | <StructureSection load='3oer' size='340' side='right'caption='[[3oer]], [[Resolution|resolution]] 3.20Å' scene=''> |
| - | You may change the PDB parameter (which sets the PDB file loaded into the applet)
| + | == Structural highlights == |
| - | or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
| + | <table><tr><td colspan='2'>[[3oer]] 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=3OER OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3OER FirstGlance]. <br> |
| - | or leave the SCENE parameter empty for the default display.
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.2Å</td></tr> |
| - | --> | + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CO:COBALT+(II)+ION'>CO</scene></td></tr> |
| - | {{STRUCTURE_3oer| PDB=3oer | SCENE= }}
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=3oer FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3oer OCA], [https://pdbe.org/3oer PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3oer RCSB], [https://www.ebi.ac.uk/pdbsum/3oer PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3oer ProSAT]</span></td></tr> |
| | + | </table> |
| | + | == Function == |
| | + | [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> |
| | + | <div style="background-color:#fffaf0;"> |
| | + | == Publication Abstract from PubMed == |
| | + | Frataxin is a mitochondrial protein with a central role in iron homeostasis. Defects in frataxin function lead to Friedreich's ataxia, a progressive neurodegenerative disease with childhood onset. The function of frataxin has been shown to be closely associated with its ability to form oligomeric species; however, the factors controlling oligomerization and the types of oligomers present in solution are a matter of debate. Using small-angle X-ray scattering, we found that Co(2+), glycerol, and a single amino acid substitution at the N-terminus, Y73A, facilitate oligomerization of yeast frataxin, resulting in a dynamic equilibrium between monomers, dimers, trimers, hexamers, and higher-order oligomers. Using X-ray crystallography, we found that Co(2+) binds inside the channel at the 3-fold axis of the trimer, which suggests that the metal has an oligomer-stabilizing role. The results reveal the types of oligomers present in solution and support our earlier suggestions that the trimer is the main building block of yeast frataxin oligomers. They also indicate that different mechanisms may control oligomer stability and oligomerization in vivo. |
| | | | |
| - | ===Crystal structure of trimeric frataxin from the yeast saccharomyces cerevisiae, complexed with cobalt===
| + | Oligomerization Propensity and Flexibility of Yeast Frataxin Studied by X-ray Crystallography and Small-Angle X-ray Scattering.,Soderberg CA, Shkumatov AV, Rajan S, Gakh O, Svergun DI, Isaya G, Al-Karadaghi S J Mol Biol. 2011 Dec 16;414(5):783-97. Epub 2011 Oct 25. PMID:22051511<ref>PMID:22051511</ref> |
| | | | |
| | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> |
| | + | </div> |
| | + | <div class="pdbe-citations 3oer" style="background-color:#fffaf0;"></div> |
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| - | <!--
| + | ==See Also== |
| - | The line below this paragraph, {{ABSTRACT_PUBMED_22051511}}, adds the Publication Abstract to the page
| + | *[[Frataxin 3D Structures|Frataxin 3D Structures]] |
| - | (as it appears on PubMed at http://www.pubmed.gov), where 22051511 is the PubMed ID number.
| + | == References == |
| - | -->
| + | <references/> |
| - | {{ABSTRACT_PUBMED_22051511}}
| + | __TOC__ |
| - | | + | </StructureSection> |
| - | ==About this Structure== | + | [[Category: Large Structures]] |
| - | [[3oer]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3OER OCA]. | + | |
| - | | + | |
| - | ==Reference== | + | |
| - | <ref group="xtra">PMID:022051511</ref><references group="xtra"/> | + | |
| | [[Category: Saccharomyces cerevisiae]] | | [[Category: Saccharomyces cerevisiae]] |
| - | [[Category: Al-Karadaghi, S.]] | + | [[Category: Al-Karadaghi S]] |
| - | [[Category: Gakh, O.]] | + | [[Category: Gakh O]] |
| - | [[Category: Isaya, G.]] | + | [[Category: Isaya G]] |
| - | [[Category: Rajan, S.]] | + | [[Category: Rajan S]] |
| - | [[Category: Soderberg, C A.G.]] | + | [[Category: Soderberg CAG]] |
| - | [[Category: Ta, C.]] | + | [[Category: Ta C]] |
| - | [[Category: Alpha/beta sandwich]]
| + | |
| - | [[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]
Publication Abstract from PubMed
Frataxin is a mitochondrial protein with a central role in iron homeostasis. Defects in frataxin function lead to Friedreich's ataxia, a progressive neurodegenerative disease with childhood onset. The function of frataxin has been shown to be closely associated with its ability to form oligomeric species; however, the factors controlling oligomerization and the types of oligomers present in solution are a matter of debate. Using small-angle X-ray scattering, we found that Co(2+), glycerol, and a single amino acid substitution at the N-terminus, Y73A, facilitate oligomerization of yeast frataxin, resulting in a dynamic equilibrium between monomers, dimers, trimers, hexamers, and higher-order oligomers. Using X-ray crystallography, we found that Co(2+) binds inside the channel at the 3-fold axis of the trimer, which suggests that the metal has an oligomer-stabilizing role. The results reveal the types of oligomers present in solution and support our earlier suggestions that the trimer is the main building block of yeast frataxin oligomers. They also indicate that different mechanisms may control oligomer stability and oligomerization in vivo.
Oligomerization Propensity and Flexibility of Yeast Frataxin Studied by X-ray Crystallography and Small-Angle X-ray Scattering.,Soderberg CA, Shkumatov AV, Rajan S, Gakh O, Svergun DI, Isaya G, Al-Karadaghi S J Mol Biol. 2011 Dec 16;414(5):783-97. Epub 2011 Oct 25. PMID:22051511[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
- ↑ Soderberg CA, Shkumatov AV, Rajan S, Gakh O, Svergun DI, Isaya G, Al-Karadaghi S. Oligomerization Propensity and Flexibility of Yeast Frataxin Studied by X-ray Crystallography and Small-Angle X-ray Scattering. J Mol Biol. 2011 Dec 16;414(5):783-97. Epub 2011 Oct 25. PMID:22051511 doi:10.1016/j.jmb.2011.10.034
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