Cited by 730Protein Structure and DynamicsGenomics and Chromatin DynamicsSignaling Pathways in Disease

Solution Structure of the KIX Domain of CBP Bound to the Transactivation Domain of CREB: A Model for Activator:Coactivator Interactions

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Radhakrishnan, Ishwar, Pérez-Alvarado, Gabriela C, Parker, David, Dyson, H.Jane, Montminy, Marc R, Wright, Peter E·1997·Cell

Abstract

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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Crossref · 10.1016/s0092-8674(00)80463-8

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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
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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