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[[Image:1hwt.gif|left|200px]]<br /><applet load="1hwt" size="350" color="white" frame="true" align="right" spinBox="true"
caption="1hwt, resolution 2.5&Aring;" />
'''STRUCTURE OF A HAP1/DNA COMPLEX REVEALS DRAMATICALLY ASYMMETRIC DNA BINDING BY A HOMODIMERIC PROTEIN'''<br />


==Overview==
==STRUCTURE OF A HAP1/DNA COMPLEX REVEALS DRAMATICALLY ASYMMETRIC DNA BINDING BY A HOMODIMERIC PROTEIN==
HAP1 is a member of a family of fungal transcription factors that contain a Zn2Cys6 binuclear cluster domain and bind as homodimers to sequences containing two DNA half sites. We have determined the 2.5 A crystal structure of HAP1 bound to a cognate upstream activation sequence from the CYC7 gene. The structure reveals that HAP1 is bound in a dramatically asymmetric manner to the DNA target. This asymmetry aligns the Zn2Cys6 domains in a tandem head-to-tail fashion to contact two DNA half sites, positions an N-terminal arm of one of the protein subunits to interact with the inter-half site base pairs in the DNA minor groove, and suggests a mechanism by which DNA-binding facilitates asymmetric dimerization by HAP1. Comparisons with the DNA complexes of the related GAL4, PPR1 and PUT3 proteins illustrate how a conserved protein domain can be reoriented to recognize DNA half sites of different polarities and how homodimeric proteins adopt dramatically asymmetric structures to recognize cognate DNA targets.
<StructureSection load='1hwt' size='340' side='right'caption='[[1hwt]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
 
== Structural highlights ==
==About this Structure==
<table><tr><td colspan='2'>[[1hwt]] is a 8 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=1HWT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1HWT FirstGlance]. <br>
1HWT is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae] with <scene name='pdbligand=ZN:'>ZN</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1HWT OCA].  
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.5&#8491;</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>
==Reference==
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1hwt FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1hwt OCA], [https://pdbe.org/1hwt PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1hwt RCSB], [https://www.ebi.ac.uk/pdbsum/1hwt PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1hwt ProSAT]</span></td></tr>
Structure of a HAP1-DNA complex reveals dramatically asymmetric DNA binding by a homodimeric protein., King DA, Zhang L, Guarente L, Marmorstein R, Nat Struct Biol. 1999 Jan;6(1):64-71. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=9886294 9886294]
</table>
== Function ==
[https://www.uniprot.org/uniprot/HAP1_YEASX HAP1_YEASX] Regulation of oxygen dependent gene expression. It modulates the expression of Iso-1 (CYP1) and Iso-2 (CYP3) cytochrome c. In response to heme, promotes transcription of genes encoding functions required for respiration, controlling oxidative damage and repression of anaerobic genes. Binds to the sequence 5'-CGGNNNTNNCGG-3'. Is non-functional in terms of iso-1 cytochrome c expression in strain S288c and its derivatives.<ref>PMID:10541856</ref> <ref>PMID:11689685</ref> <ref>PMID:2851658</ref> <ref>PMID:9027731</ref>
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/hw/1hwt_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </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/main_output.php?pdb_ID=1hwt ConSurf].
<div style="clear:both"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Saccharomyces cerevisiae]]
[[Category: Saccharomyces cerevisiae]]
[[Category: Single protein]]
[[Category: Guarente L]]
[[Category: Guarente, L.]]
[[Category: King DA]]
[[Category: King, D A.]]
[[Category: Marmorstein R]]
[[Category: Marmorstein, R.]]
[[Category: Zhang L]]
[[Category: Zhang, L.]]
[[Category: ZN]]
[[Category: asymmetry]]
[[Category: complex activator/dna]]
[[Category: gal4]]
[[Category: transcription factor]]
 
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