From Proteopedia
(Difference between revisions)
proteopedia linkproteopedia link
|
|
| Line 1: |
Line 1: |
| - | [[Image:1nwq.gif|left|200px]] | + | {{Seed}} |
| | + | [[Image:1nwq.png|left|200px]] |
| | | | |
| | <!-- | | <!-- |
| Line 9: |
Line 10: |
| | {{STRUCTURE_1nwq| PDB=1nwq | SCENE= }} | | {{STRUCTURE_1nwq| PDB=1nwq | SCENE= }} |
| | | | |
| - | '''CRYSTAL STRUCTURE OF C/EBPALPHA-DNA COMPLEX'''
| + | ===CRYSTAL STRUCTURE OF C/EBPALPHA-DNA COMPLEX=== |
| | | | |
| | | | |
| - | ==Overview==
| + | <!-- |
| - | 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.
| + | The line below this paragraph, {{ABSTRACT_PUBMED_12578822}}, adds the Publication Abstract to the page |
| | + | (as it appears on PubMed at http://www.pubmed.gov), where 12578822 is the PubMed ID number. |
| | + | --> |
| | + | {{ABSTRACT_PUBMED_12578822}} |
| | | | |
| | ==About this Structure== | | ==About this Structure== |
| Line 29: |
Line 33: |
| | [[Category: Basic leucine zipper]] | | [[Category: Basic leucine zipper]] |
| | [[Category: Protein-dna complex]] | | [[Category: Protein-dna complex]] |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 03:04:18 2008'' | + | |
| | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 15:26:36 2008'' |
Revision as of 12:26, 27 July 2008
Template:STRUCTURE 1nwq
CRYSTAL STRUCTURE OF C/EBPALPHA-DNA COMPLEX
Template:ABSTRACT PUBMED 12578822
About this Structure
1NWQ is a Single protein structure of sequence from Rattus norvegicus. Full crystallographic information is available from 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:12578822
Page seeded by OCA on Sun Jul 27 15:26:36 2008
