title: Structural insights into interactions of C/EBP transcriptional activators with the Taz2 domain of p300.
abstract: Members of the C/EBP family of transcription factors bind to the Taz2 domain of p300/CBP and mediate its phosphorylation through the recruitment of specific kinases. Short sequence motifs termed homology boxes A and B, which comprise their minimal transactivation domains (TADs), are conserved between C/EBP activators and are necessary for specific p300/CBP binding. A possible mode of interaction between C/EBP TADs and the p300 Taz2 domain was implied by the crystal structure of a chimeric protein composed of residues 1723-1818 of p300 Taz2 and residues 37-61 of C/EBPℇ. The segment corresponding to the C/EBPℇ TAD forms two orthogonally disposed helices connected by a short linker and interacts with the core structure of Taz2 from a symmetry-related molecule. It is proposed that other members of the C/EBP family interact with the Taz2 domain in the same manner. The position of the C/EBPℇ peptide on the Taz2 protein interaction surface suggests that the N-termini of C/EBP proteins are unbound in the C/EBP-p300 Taz2 complex. This observation is in agreement with the known location of the docking site of protein kinase HIPK2 in the C/EBPβ N-terminus, which associates with the C/EBPβ-p300 complex.
authors.affiliation: Protein Structure Section, Macromolecular Crystallography Laboratory, National Cancer Institute at Frederick, Frederick, MD 21702, USA.
authors.forename: Prasenjit
authors.initials: P
authors.lastname: Bhaumik
authors.affiliation: Protein Structure Section, Macromolecular Crystallography Laboratory, National Cancer Institute at Frederick, Frederick, MD 21702, USA.
authors.forename: Jamaine
authors.initials: J
authors.lastname: Davis
authors.affiliation: Protein Purification Core, Macromolecular Crystallography Laboratory, National Cancer Institute at Frederick, Frederick, MD 21702, USA.
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Tropea
authors.affiliation: Protein Purification Core, Macromolecular Crystallography Laboratory, National Cancer Institute at Frederick, Frederick, MD 21702, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Cherry
authors.affiliation: Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute at Frederick, Frederick, MD 21702, USA.
authors.forename: Peter F
authors.initials: PF
authors.lastname: Johnson
authors.affiliation: Protein Structure Section, Macromolecular Crystallography Laboratory, National Cancer Institute at Frederick, Frederick, MD 21702, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Miller
mesh_terms: D000595:Amino Acid Sequence; D022762:CCAAT-Enhancer-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D018360:Crystallography, X-Ray; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011487:Protein Conformation; D017386:Sequence Homology, Amino Acid; D050880:p300-CBP Transcription Factors / Q000737:chemistry*
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; D050880:p300-CBP Transcription Factors
keywords: HIPK2; ligand binding; molecular recognition; transcription