1jk2: Difference between revisions

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New page: left|200px<br /><applet load="1jk2" size="450" color="white" frame="true" align="right" spinBox="true" caption="1jk2, resolution 1.65Å" /> '''Zif268 D20A mutant b...
 
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[[Image:1jk2.gif|left|200px]]<br /><applet load="1jk2" size="450" color="white" frame="true" align="right" spinBox="true"
caption="1jk2, resolution 1.65&Aring;" />
'''Zif268 D20A mutant bound to the GCT DNA site'''<br />


==Overview==
==Zif268 D20A mutant bound to the GCT DNA site==
Structural and biochemical studies of Cys(2)His(2) zinc finger proteins, initially led several groups to propose a "recognition code" involving a, simple set of rules relating key amino acid residues in the zinc finger, protein to bases in its DNA site. One recent study from our group, involving geometric analysis of protein-DNA interactions, has discussed, limitations of this idea and has shown how the spatial relationship, between the polypeptide backbone and the DNA helps to determine what, contacts are possible at any given position in a protein-DNA complex. Here, we report a study of a zinc finger variant that highlights yet another, source of complexity inherent in protein-DNA recognition. In particular, we find that mutations can cause key side-chains to rearrange at the, protein-DNA interface without fundamental changes in the spatial, relationship between the polypeptide backbone and the DNA. This is clear, from a simple analysis of the binding site preferences and co-crystal, structures for the Asp20--&gt;Ala point mutant of Zif268. This point mutation, in finger one changes the specificity of the protein from GCG TGG GCG to, GCG TGG GC(G/T), and we have solved crystal structures of the D20A mutant, bound to both types of sites. The structure of the D20A mutant bound to, the GCG site reveals that contacts from key residues in the recognition, helix are coupled in complex ways. The structure of the complex with the, GCT site also shows an important new water molecule at the protein-DNA, interface. These side-chain/side-chain interactions, and resultant changes, in hydration at the interface, affect binding specificity in ways that, cannot be predicted either from a simple recognition code or from analysis, of spatial relationships at the protein-DNA interface. Accurate computer, modeling of protein-DNA interfaces remains a challenging problem and will, require systematic strategies for modeling side-chain rearrangements and, change in hydration.
<StructureSection load='1jk2' size='340' side='right'caption='[[1jk2]], [[Resolution|resolution]] 1.65&Aring;' scene=''>
 
== Structural highlights ==
==About this Structure==
<table><tr><td colspan='2'>[[1jk2]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1JK2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1JK2 FirstGlance]. <br>
1JK2 is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus] with ZN as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1JK2 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]] 1.65&#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=1jk2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1jk2 OCA], [https://pdbe.org/1jk2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1jk2 RCSB], [https://www.ebi.ac.uk/pdbsum/1jk2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1jk2 ProSAT]</span></td></tr>
Rearrangement of side-chains in a Zif268 mutant highlights the complexities of zinc finger-DNA recognition., Miller JC, Pabo CO, J Mol Biol. 2001 Oct 19;313(2):309-15. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11800559 11800559]
</table>
== Function ==
[https://www.uniprot.org/uniprot/EGR1_MOUSE EGR1_MOUSE] Transcriptional regulator. Recognizes and binds to the DNA sequence 5'-CGCCCCCGC-3'(EGR-site). Activates the transcription of target genes whose products are required for mitogenesis and differentiation.
== 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/jk/1jk2_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=1jk2 ConSurf].
<div style="clear:both"></div>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Mus musculus]]
[[Category: Single protein]]
[[Category: Miller JC]]
[[Category: Miller, J.C.]]
[[Category: Pabo CO]]
[[Category: Pabo, C.O.]]
[[Category: ZN]]
[[Category: double stranded dna]]
[[Category: protein-dna complex]]
[[Category: zinc-finger]]
 
''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 18:20:16 2007''

Latest revision as of 10:40, 7 February 2024

Zif268 D20A mutant bound to the GCT DNA siteZif268 D20A mutant bound to the GCT DNA site

Structural highlights

1jk2 is a 3 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:X-ray diffraction, Resolution 1.65Å
Ligands:
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

EGR1_MOUSE Transcriptional regulator. Recognizes and binds to the DNA sequence 5'-CGCCCCCGC-3'(EGR-site). Activates the transcription of target genes whose products are required for mitogenesis and differentiation.

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

1jk2, resolution 1.65Å

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA
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