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http://purl.uniprot.org/citations/12578822http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/12578822http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/12578822http://www.w3.org/2000/01/rdf-schema#comment"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."xsd:string
http://purl.uniprot.org/citations/12578822http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m300417200"xsd:string
http://purl.uniprot.org/citations/12578822http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m300417200"xsd:string
http://purl.uniprot.org/citations/12578822http://purl.uniprot.org/core/author"Dauter Z."xsd:string
http://purl.uniprot.org/citations/12578822http://purl.uniprot.org/core/author"Dauter Z."xsd:string
http://purl.uniprot.org/citations/12578822http://purl.uniprot.org/core/author"Miller M."xsd:string
http://purl.uniprot.org/citations/12578822http://purl.uniprot.org/core/author"Miller M."xsd:string
http://purl.uniprot.org/citations/12578822http://purl.uniprot.org/core/author"Johnson P.F."xsd:string
http://purl.uniprot.org/citations/12578822http://purl.uniprot.org/core/author"Johnson P.F."xsd:string
http://purl.uniprot.org/citations/12578822http://purl.uniprot.org/core/author"Sebastian T."xsd:string
http://purl.uniprot.org/citations/12578822http://purl.uniprot.org/core/author"Sebastian T."xsd:string
http://purl.uniprot.org/citations/12578822http://purl.uniprot.org/core/author"Shuman J.D."xsd:string
http://purl.uniprot.org/citations/12578822http://purl.uniprot.org/core/author"Shuman J.D."xsd:string
http://purl.uniprot.org/citations/12578822http://purl.uniprot.org/core/date"2003"xsd:gYear
http://purl.uniprot.org/citations/12578822http://purl.uniprot.org/core/date"2003"xsd:gYear
http://purl.uniprot.org/citations/12578822http://purl.uniprot.org/core/name"J. Biol. Chem."xsd:string
http://purl.uniprot.org/citations/12578822http://purl.uniprot.org/core/name"J. Biol. Chem."xsd:string
http://purl.uniprot.org/citations/12578822http://purl.uniprot.org/core/pages"15178-15184"xsd:string
http://purl.uniprot.org/citations/12578822http://purl.uniprot.org/core/pages"15178-15184"xsd:string
http://purl.uniprot.org/citations/12578822http://purl.uniprot.org/core/title"Structural basis for DNA recognition by the basic region leucine zipper transcription factor CCAAT/enhancer-binding protein alpha."xsd:string
http://purl.uniprot.org/citations/12578822http://purl.uniprot.org/core/title"Structural basis for DNA recognition by the basic region leucine zipper transcription factor CCAAT/enhancer-binding protein alpha."xsd:string
http://purl.uniprot.org/citations/12578822http://purl.uniprot.org/core/volume"278"xsd:string
http://purl.uniprot.org/citations/12578822http://purl.uniprot.org/core/volume"278"xsd:string
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