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 α helices. The amphipathic helix αB of pKID interacts with a hydrophobic groove defined by helices αl and α3 of KIX. The other pKID helix, αA, contacts a different face of the α3 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 741-752 |
| Number of pages | 12 |
| Journal | Cell |
| Volume | 91 |
| Issue number | 6 |
| DOIs | |
| State | Published - Dec 12 1997 |
Funding
We thank Drs. Mark Foster, David Case, Danilo Casimiro, Signe Holmbeck, Xiang Li, and John Chung for valuable discussions and assistance; Dr. Susan Taylor for providing kinase; Martine Reymond and Linda Tennant for technical assistance; Michael Pique for assistance with graphics; and MSI for access to NMR software. This work was supported by grants from the National Institutes of Health (P. E. W. and M. R. M.), the Skaggs Institute for Chemical Biology (P. E. W.), and the Iacocca Foundation (M. R. M. and D. P.). I. R. and G. C. P. A. were supported by the Jane Coffin Childs Foundation and the Leukemia Society of America.
ASJC Scopus subject areas
- General Biochemistry, Genetics and Molecular Biology