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| | ==SOLUTION NMR STRUCTURE OF THE L22V MUTANT DNA BINDING DOMAIN OF AREA COMPLEXED TO A 13 BP DNA CONTAINING A TGATA SITE, REGULARIZED MEAN STRUCTURE== | | ==SOLUTION NMR STRUCTURE OF THE L22V MUTANT DNA BINDING DOMAIN OF AREA COMPLEXED TO A 13 BP DNA CONTAINING A TGATA SITE, REGULARIZED MEAN STRUCTURE== |
| - | <StructureSection load='6gat' size='340' side='right'caption='[[6gat]], [[NMR_Ensembles_of_Models | 1 NMR models]]' scene=''> | + | <StructureSection load='6gat' size='340' side='right'caption='[[6gat]]' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[6gat]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/A._nidulans A. nidulans]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GAT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6GAT FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[6gat]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Aspergillus_nidulans Aspergillus nidulans]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6GAT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6GAT 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> | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[7gat|7gat]]</div></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">POTENTIAL ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=162425 A. nidulans])</td></tr>
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| | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6gat FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gat OCA], [https://pdbe.org/6gat PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6gat RCSB], [https://www.ebi.ac.uk/pdbsum/6gat PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6gat ProSAT]</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=6gat FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6gat OCA], [https://pdbe.org/6gat PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6gat RCSB], [https://www.ebi.ac.uk/pdbsum/6gat PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6gat ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/AREA_EMENI AREA_EMENI]] Transcription activator that binds the consensus DNA element 5'-CGATAG-3' and mediates nitrogen metabolite repression. Activates the transcription of uapA.<ref>PMID:1970293</ref>
| + | [https://www.uniprot.org/uniprot/AREA_EMENI AREA_EMENI] Transcription activator that binds the consensus DNA element 5'-CGATAG-3' and mediates nitrogen metabolite repression. Activates the transcription of uapA.<ref>PMID:1970293</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: A. nidulans]] | + | [[Category: Aspergillus nidulans]] |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Clore, G M]] | + | [[Category: Clore GM]] |
| - | [[Category: Gronenborn, A M]] | + | [[Category: Gronenborn AM]] |
| - | [[Category: Starich, M]] | + | [[Category: Starich M]] |
| - | [[Category: Wikstrom, M]] | + | [[Category: Wikstrom M]] |
| - | [[Category: Dna binding protein]]
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| - | [[Category: Transcription factor]]
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| - | [[Category: Transcription-dna complex]]
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| - | [[Category: Zinc binding domain]]
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| Structural highlights
Function
AREA_EMENI Transcription activator that binds the consensus DNA element 5'-CGATAG-3' and mediates nitrogen metabolite repression. Activates the transcription of uapA.[1]
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
The seemingly innocuous leucine-to-valine mutation at position 22 of the AREA DNA binding domain results in dramatic changes in the in vivo expression profile of genes controlled by this GATA transcription factor. This is associated with a preference of the Leu22-->Val mutant for TGATAG sites over (A/C)GATAG sites. Quantitative gel retardation assays confirm this observation and show that the Leu22-->Val mutant AREA DNA binding domain has a approximately 30-fold lower affinity than the wild-type domain for a 13 base-pair oligonucleotide containing the wild-type CGATAG target. To gain insight into the measured affinity data and further explore sequence specificity of the AREA protein, the solution structure of a complex between the Leu22-->Val mutant AREA DNA binding domain and a 13 base-pair oligonucleotide containing its physiologically relevant TGATAG target sequence has been determined by multidimensional nuclear magnetic resonance spectroscopy. Comparison of this structure with that of the wild-type AREA DNA binding domain complexed to its cognate CGATAG target site shows how subtle changes in amino acid side-chain length and hydrophobic packing can affect affinity and specificity for GATA-containing sequences, and how changes in DNA sequence can be compensated for by changes in protein sequence.
The solution structure of the Leu22-->Val mutant AREA DNA binding domain complexed with a TGATAG core element defines a role for hydrophobic packing in the determination of specificity.,Starich MR, Wikstrom M, Schumacher S, Arst HN Jr, Gronenborn AM, Clore GM J Mol Biol. 1998 Apr 3;277(3):621-34. PMID:9533884[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Kudla B, Caddick MX, Langdon T, Martinez-Rossi NM, Bennett CF, Sibley S, Davies RW, Arst HN Jr. The regulatory gene areA mediating nitrogen metabolite repression in Aspergillus nidulans. Mutations affecting specificity of gene activation alter a loop residue of a putative zinc finger. EMBO J. 1990 May;9(5):1355-64. PMID:1970293
- ↑ Starich MR, Wikstrom M, Schumacher S, Arst HN Jr, Gronenborn AM, Clore GM. The solution structure of the Leu22-->Val mutant AREA DNA binding domain complexed with a TGATAG core element defines a role for hydrophobic packing in the determination of specificity. J Mol Biol. 1998 Apr 3;277(3):621-34. PMID:9533884 doi:10.1006/jmbi.1997.1626
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