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| ==Crystal structure of AFT2 in complex with DNA== | | ==Crystal structure of AFT2 in complex with DNA== |
- | <StructureSection load='4lmg' size='340' side='right' caption='[[4lmg]], [[Resolution|resolution]] 2.20Å' scene=''> | + | <StructureSection load='4lmg' size='340' side='right'caption='[[4lmg]], [[Resolution|resolution]] 2.20Å' scene=''> |
| == Structural highlights == | | == Structural highlights == |
- | <table><tr><td colspan='2'>[[4lmg]] is a 8 chain structure with sequence from [http://en.wikipedia.org/wiki/Baker's_yeast Baker's yeast]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LMG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4LMG FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4lmg]] is a 8 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4LMG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4LMG 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='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='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">AFT2, YPL202C ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=559292 Baker's yeast])</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=4lmg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lmg OCA], [https://pdbe.org/4lmg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4lmg RCSB], [https://www.ebi.ac.uk/pdbsum/4lmg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4lmg ProSAT]</span></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=4lmg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4lmg OCA], [http://pdbe.org/4lmg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4lmg RCSB], [http://www.ebi.ac.uk/pdbsum/4lmg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4lmg ProSAT]</span></td></tr> | + | |
| </table> | | </table> |
| == Function == | | == Function == |
- | [[http://www.uniprot.org/uniprot/AFT2_YEAST AFT2_YEAST]] Transcription factor required for iron homeostasis and resistance to oxidative stress. With RCS1, activates the gene expression in response to low-iron conditions, also called iron regulon.<ref>PMID:11448968</ref> <ref>PMID:11734641</ref> <ref>PMID:12756250</ref> <ref>PMID:15649888</ref> <ref>PMID:16024809</ref> | + | [https://www.uniprot.org/uniprot/AFT2_YEAST AFT2_YEAST] Transcription factor required for iron homeostasis and resistance to oxidative stress. With RCS1, activates the gene expression in response to low-iron conditions, also called iron regulon.<ref>PMID:11448968</ref> <ref>PMID:11734641</ref> <ref>PMID:12756250</ref> <ref>PMID:15649888</ref> <ref>PMID:16024809</ref> |
| <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| ==See Also== | | ==See Also== |
- | *[[Transcriptional activator|Transcriptional activator]] | + | *[[Transcriptional activator 3D structures|Transcriptional activator 3D structures]] |
| == References == | | == References == |
| <references/> | | <references/> |
| __TOC__ | | __TOC__ |
| </StructureSection> | | </StructureSection> |
- | [[Category: Baker's yeast]] | + | [[Category: Large Structures]] |
- | [[Category: He, C]] | + | [[Category: Saccharomyces cerevisiae S288C]] |
- | [[Category: Poor, C B]] | + | [[Category: He C]] |
- | [[Category: Sanishvili, R]] | + | [[Category: Poor CB]] |
- | [[Category: Schuermann, J P]] | + | [[Category: Sanishvili R]] |
- | [[Category: Dna binding]] | + | [[Category: Schuermann JP]] |
- | [[Category: Iron binding]]
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- | [[Category: Transcription activator-dna complex]]
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- | [[Category: Transcription factor]]
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- | [[Category: Wrky-gcm1]]
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- | [[Category: Wrky-gcm1 fold]]
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| Structural highlights
Function
AFT2_YEAST Transcription factor required for iron homeostasis and resistance to oxidative stress. With RCS1, activates the gene expression in response to low-iron conditions, also called iron regulon.[1] [2] [3] [4] [5]
Publication Abstract from PubMed
The paralogous iron-responsive transcription factors Aft1 and Aft2 (activators of ferrous transport) regulate iron homeostasis in Saccharomyces cerevisiae by activating expression of iron-uptake and -transport genes when intracellular iron is low. We present the previously unidentified crystal structure of Aft2 bound to DNA that reveals the mechanism of DNA recognition via specific interactions of the iron-responsive element with a Zn(2+)-containing WRKY-GCM1 domain in Aft2. We also show that two Aft2 monomers bind a [2Fe-2S] cluster (or Fe(2+)) through a Cys-Asp-Cys motif, leading to dimerization of Aft2 and decreased DNA-binding affinity. Furthermore, we demonstrate that the [2Fe-2S]-bridged heterodimer formed between glutaredoxin-3 and the BolA-like protein Fe repressor of activation-2 transfers a [2Fe-2S] cluster to Aft2 that facilitates Aft2 dimerization. Previous in vivo findings strongly support the [2Fe-2S] cluster-induced dimerization model; however, given the available evidence, Fe(2+)-induced Aft2 dimerization cannot be completely ruled out as an alternative Aft2 inhibition mechanism. Taken together, these data provide insight into the molecular mechanism for iron-dependent transcriptional regulation of Aft2 and highlight the key role of Fe-S clusters as cellular iron signals.
Molecular mechanism and structure of the Saccharomyces cerevisiae iron regulator Aft2.,Poor CB, Wegner SV, Li H, Dlouhy AC, Schuermann JP, Sanishvili R, Hinshaw JR, Riggs-Gelasco PJ, Outten CE, He C Proc Natl Acad Sci U S A. 2014 Mar 18;111(11):4043-8. doi:, 10.1073/pnas.1318869111. Epub 2014 Mar 3. PMID:24591629[6]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Blaiseau PL, Lesuisse E, Camadro JM. Aft2p, a novel iron-regulated transcription activator that modulates, with Aft1p, intracellular iron use and resistance to oxidative stress in yeast. J Biol Chem. 2001 Sep 7;276(36):34221-6. Epub 2001 Jul 11. PMID:11448968 doi:http://dx.doi.org/10.1074/jbc.M104987200
- ↑ Rutherford JC, Jaron S, Ray E, Brown PO, Winge DR. A second iron-regulatory system in yeast independent of Aft1p. Proc Natl Acad Sci U S A. 2001 Dec 4;98(25):14322-7. PMID:11734641 doi:http://dx.doi.org/10.1073/pnas.261381198
- ↑ Rutherford JC, Jaron S, Winge DR. Aft1p and Aft2p mediate iron-responsive gene expression in yeast through related promoter elements. J Biol Chem. 2003 Jul 25;278(30):27636-43. Epub 2003 May 19. PMID:12756250 doi:http://dx.doi.org/10.1074/jbc.M300076200
- ↑ Rutherford JC, Ojeda L, Balk J, Muhlenhoff U, Lill R, Winge DR. Activation of the iron regulon by the yeast Aft1/Aft2 transcription factors depends on mitochondrial but not cytosolic iron-sulfur protein biogenesis. J Biol Chem. 2005 Mar 18;280(11):10135-40. Epub 2005 Jan 13. PMID:15649888 doi:http://dx.doi.org/10.1074/jbc.M413731200
- ↑ Courel M, Lallet S, Camadro JM, Blaiseau PL. Direct activation of genes involved in intracellular iron use by the yeast iron-responsive transcription factor Aft2 without its paralog Aft1. Mol Cell Biol. 2005 Aug;25(15):6760-71. PMID:16024809 doi:http://dx.doi.org/25/15/6760
- ↑ Poor CB, Wegner SV, Li H, Dlouhy AC, Schuermann JP, Sanishvili R, Hinshaw JR, Riggs-Gelasco PJ, Outten CE, He C. Molecular mechanism and structure of the Saccharomyces cerevisiae iron regulator Aft2. Proc Natl Acad Sci U S A. 2014 Mar 18;111(11):4043-8. doi:, 10.1073/pnas.1318869111. Epub 2014 Mar 3. PMID:24591629 doi:http://dx.doi.org/10.1073/pnas.1318869111
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