1nwq: Difference between revisions

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Revision as of 14:02, 20 March 2008

File:1nwq.gif

, resolution 2.80Å

Gene:

CEBPA (Rattus norvegicus)

Coordinates:

save as pdb, mmCIF, xml

CRYSTAL STRUCTURE OF C/EBPALPHA-DNA COMPLEX

OverviewOverview

CCAAT/enhancer-binding proteins (C/EBPs) are basic region leucine zipper (bZIP) transcription factors that regulate cell differentiation, growth, survival, and inflammation. To understand the molecular basis of DNA recognition by the C/EBP family we determined the x-ray structure of a C/EBPalpha bZIP polypeptide bound to its cognate DNA site (A(-5)T(-4)T(-3)G(-2)C(-1)G(1)C(2)A(3)A(4)T(5)) and characterized several basic region mutants. Binding specificity is provided by interactions of basic region residues Arg(289), Asn(292), Ala(295), Val(296), Ser(299), and Arg(300) with DNA bases. A striking feature of the C/EBPalpha protein-DNA interface that distinguishes it from known bZIP-DNA complexes is the central role of Arg(289), which is hydrogen-bonded to base A(3), phosphate, Asn(292) (invariant in bZIPs), and Asn(293). The conformation of Arg(289) is also restricted by Tyr(285). In accordance with the structural model, mutation of Arg(289) or a pair of its interacting partners (Tyr(285) and Asn(293)) abolished C/EBPalpha binding activity. Val(296) (Ala in most other bZIPs) contributes to C/EBPalpha specificity by discriminating against purines at position -3 and imposing steric restraints on the invariant Arg(300). Mutating Val(296) to Ala strongly enhanced C/EBPalpha binding to cAMP response element (CRE) sites while retaining affinity for C/EBP sites. Thus, Arg(289) is essential for formation of the complementary protein-DNA interface, whereas Val(296) functions primarily to restrict interactions with related sequences such as CRE sites rather than specifying binding to C/EBP sites. Our studies also help to explain the phenotypes of mice carrying targeted mutations in the C/EBPalpha bZIP region.

About this StructureAbout this Structure

1NWQ is a Single protein structure of sequence from Rattus norvegicus. Full crystallographic information is available from OCA.

ReferenceReference

Structural basis for DNA recognition by the basic region leucine zipper transcription factor CCAAT/enhancer-binding protein alpha., Miller M, Shuman JD, Sebastian T, Dauter Z, Johnson PF, J Biol Chem. 2003 Apr 25;278(17):15178-84. Epub 2003 Feb 10. PMID:12578822

Page seeded by OCA on Thu Mar 20 13:02:41 2008

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

OCA

@@ Line 1: / Line 1: @@
-[[Image:1nwq.gif|left|200px]]<br /><applet load="1nwq" size="350" color="white" frame="true" align="right" spinBox="true"
+[[Image:1nwq.gif|left|200px]]
-caption="1nwq, resolution 2.80&Aring;" />
-'''CRYSTAL STRUCTURE OF C/EBPALPHA-DNA COMPLEX'''<br />
+ {{Structure
+|PDB= 1nwq |SIZE=350|CAPTION= <scene name='initialview01'>1nwq</scene>, resolution 2.80&Aring;
+|SITE=
+|LIGAND=
+|ACTIVITY=
+|GENE= CEBPA ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Rattus norvegicus])
+}}
+'''CRYSTAL STRUCTURE OF C/EBPALPHA-DNA COMPLEX'''
 ==Overview==
@@ Line 7: / Line 16: @@
 ==About this Structure==
-NWQ is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NWQ OCA].
+NWQ is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1NWQ OCA].
 ==Reference==
-Structural basis for DNA recognition by the basic region leucine zipper transcription factor CCAAT/enhancer-binding protein alpha., Miller M, Shuman JD, Sebastian T, Dauter Z, Johnson PF, J Biol Chem. 2003 Apr 25;278(17):15178-84. Epub 2003 Feb 10. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=12578822 12578822]
+Structural basis for DNA recognition by the basic region leucine zipper transcription factor CCAAT/enhancer-binding protein alpha., Miller M, Shuman JD, Sebastian T, Dauter Z, Johnson PF, J Biol Chem. 2003 Apr 25;278(17):15178-84. Epub 2003 Feb 10. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/12578822 12578822]
 [[Category: Rattus norvegicus]]
 [[Category: Single protein]]
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 [[Category: protein-dna complex]]
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 14:10:53 2008''
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 13:02:41 2008''