Abstract
Structure-based mutagenesis was used to probe the binding surface for the activation domain of sterol-responsive element binding protein (SREBP) in the KIX domain of CREB binding protein. A set of conserved residues scattering in the alpha2 helix and the extended C-terminal region of alpha 3 helix in the KIX domain including two arginines previously characterized as a hot spot for cofactor-mediated methylation was shown to be crucial for SREBP-KIX interaction, and was not essential for phosphorylated KID recognition. Therefore, our results suggest the existence of a SREBP binding site formed by positively charged residues in the C-terminal part of the extended alpha 3 helix of the KIX domain distinct from the previously identified phosphorylated KID binding site.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Base Sequence
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Binding Sites
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CCAAT-Enhancer-Binding Proteins / metabolism*
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CREB-Binding Protein
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Cyclic AMP Response Element-Binding Protein / genetics
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Cyclic AMP Response Element-Binding Protein / metabolism
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DNA-Binding Proteins / metabolism*
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Humans
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Models, Molecular
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Molecular Sequence Data
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Mutagenesis
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Nuclear Proteins / chemistry
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Nuclear Proteins / genetics*
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Nuclear Proteins / metabolism*
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Oligonucleotides / genetics
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Protein Binding
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Protein Structure, Secondary
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Protein Structure, Tertiary
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Proto-Oncogene Proteins c-myb / genetics
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Proto-Oncogene Proteins c-myb / metabolism
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Recombinant Fusion Proteins / chemistry
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Sequence Alignment
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Sterol Regulatory Element Binding Protein 1
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Trans-Activators / chemistry
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Trans-Activators / genetics*
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Trans-Activators / metabolism*
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Transcription Factors*
Substances
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CCAAT-Enhancer-Binding Proteins
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Cyclic AMP Response Element-Binding Protein
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DNA-Binding Proteins
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Nuclear Proteins
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Oligonucleotides
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Proto-Oncogene Proteins c-myb
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Recombinant Fusion Proteins
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SREBF1 protein, human
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Sterol Regulatory Element Binding Protein 1
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Trans-Activators
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Transcription Factors
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CREB-Binding Protein
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CREBBP protein, human