4lmg: Difference between revisions

Revision as of 03:42, 25 December 2014

Crystal structure of AFT2 in complex with DNA

Structural highlights

4lmg is a 8 chain structure with sequence from Baker's yeast. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:	ZN
Gene:	AFT2, YPL202C (Baker's yeast)
Resources:	FirstGlance, OCA, RCSB, PDBsum

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.

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:https://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:https://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:https://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:https://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:https://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:https://dx.doi.org/10.1073/pnas.1318869111

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OCA

[1] 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:https://dx.doi.org/10.1074/jbc.M104987200

[2] 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:https://dx.doi.org/10.1073/pnas.261381198

[3] 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:https://dx.doi.org/10.1074/jbc.M300076200

[4] 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:https://dx.doi.org/10.1074/jbc.M413731200

[5] 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:https://dx.doi.org/25/15/6760

[6] 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:https://dx.doi.org/10.1073/pnas.1318869111

[1]

[2]

[3]

[4]

[5]

[6]

@@ Line 3: / Line 3: @@
 == 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>
-</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=ZN:ZINC+ION'>ZN</scene><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>
-<tr><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='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><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://www.rcsb.org/pdb/explore.do?structureId=4lmg RCSB], [http://www.ebi.ac.uk/pdbsum/4lmg PDBsum]</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://www.rcsb.org/pdb/explore.do?structureId=4lmg RCSB], [http://www.ebi.ac.uk/pdbsum/4lmg PDBsum]</span></td></tr>
-<table>
+</table>
+== 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>
 <div style="background-color:#fffaf0;">
 == Publication Abstract from PubMed ==
@@ Line 13: / Line 15: @@
 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<ref>PMID:24591629</ref>
-From MEDLINEÂ®/PubMedÂ®, a database of the U.S. National Library of Medicine.<br>
+From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+==See Also==
+*[[Transcriptional activator|Transcriptional activator]]
 == References ==
 <references/>
@@ Line 20: / Line 25: @@
 </StructureSection>
 [[Category: Baker's yeast]]
-[[Category: He, C.]]
+[[Category: He, C]]
-[[Category: Poor, C B.]]
+[[Category: Poor, C B]]
-[[Category: Sanishvili, R.]]
+[[Category: Sanishvili, R]]
-[[Category: Schuermann, J P.]]
+[[Category: Schuermann, J P]]
 [[Category: Dna binding]]
 [[Category: Iron binding]]

4lmg: Difference between revisions

Revision as of 03:42, 25 December 2014

Crystal structure of AFT2 in complex with DNA

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

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