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Solution Structure of the KIX Domain of CBP Bound to the Transactivation Domain of CREB: A Model for Activator:Coactivator Interactions
Open accessAbstract
The nuclear factor CREB activates transcription of target genes in part through direct interactions with the KIX domain of the coactivator CBP in a phosphorylation-dependent manner. The solution structure of the complex formed by the phosphorylated kinase-inducible domain (pKID) of CREB with KIX reveals that pKID undergoes a coil-->helix folding transition upon binding to KIX, forming two alpha helices. The amphipathic helix alphaB of pKID interacts with a hydrophobic groove defined by helices alpha1 and alpha3 of KIX. The other pKID helix, alphaA, contacts a different face of the alpha3 helix. The phosphate group of the critical phosphoserine residue of pKID forms a hydrogen bond to the side chain of Tyr-658 of KIX. The structure provides a model for interactions between other transactivation domains and their targets.
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“a single hydrogen bond between this phosphoserine and a tyrosine residue within CBP is critical for complexation”
From Assembly requirements of PU.1–Pip (IRF‐4) activator complexes: inhibiting function in vivo using fused dimers (1999) · cites this paper as Radhakrishnan et al., 1997
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Metadata
- Authors
- Radhakrishnan, I., Pérez-Alvarado, G. C., Parker, D., Dyson, H. J., Montminy, M. R., & Wright, P. E.
- Affiliations
- Scripps Research Institute (US)
- Joslin Diabetes Center (US)
- Corresponding author
- Wright, Peter E
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 1997-12
- Volume
- 91
- Issue
- 6
- Pages
- 741-752
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W1968910000
- Cited by
- 728
- References
- 59
- Citations by year
- 2026: 11 · 2025: 18 · 2024: 10 · 2023: 17 · 2022: 20 · 2021: 14 · 2020: 19 · 2019: 19 · 2018: 25 · 2017: 24 · 2016: 29 · 2015: 23 · 2014: 30 · 2013: 27 · 2012: 32
- FWCI
- 10.19
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Signaling Pathways in Disease
- Keywords
- CREB, CBP, KIX domain, transactivation domain, transcriptional coactivator, protein-protein interaction, amphipathic helix, hydrophobic groove, transcriptional activation, solution structure
- MeSH terms
- Amino Acid Sequence, Animals, Binding Sites, Humans, Models, Molecular, Molecular Sequence Data, Nuclear Proteins, Phosphopeptides, Protein Conformation, Transcription Factors, Trans-Activators, Consensus Sequence, Sequence Alignment, Cyclic AMP Response Element-Binding Protein, Sequence Homology, Amino Acid, Protein Structure, Secondary, Nuclear Magnetic Resonance, Biomolecular, CREB-Binding Protein
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