Abstract
Phosphorylation of Ser133 within the kinase inducible transactivation domain (KID) of the transcription factor CREB potentiates interaction with the KIX domain of coactivator CBP. Heteronuclear NMR spectroscopic analyses reveal that the KID domain is largely unstructured except for residues that comprise the αA helix in the pKID-KIX complex, which populate helical conformations to a significant extent (>50%). The helical content in the αB region is very small in the non-phosphorylated form (~ 10%) although a small increase is detected upon Ser133 phosphorylation. The intrinsic bias towards helical conformations probably facilitates folding of the KID domain upon binding to KIX while the principal role of the phosphate group appears to be largely in mediating the intermolecular interactions in the pKID-KIX complex.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 317-322 |
| Number of pages | 6 |
| Journal | FEBS Letters |
| Volume | 430 |
| Issue number | 3 |
| DOIs | |
| State | Published - Jul 3 1998 |
Funding
We thank Drs. David Eliezer and Marc Montminy for valuable discussions, Dr. Susan Taylor for providing protein kinase-A, and Molecular Simulations Inc. (San Diego, CA) for access to NMR software. This work was supported by grants from the National Institutes of Health and the Skaggs Institute for Chemical Biology. I.R. and G.C.P.A. acknowledge support from the Jane Coffin Childs Foundation and the Leukemia Society of America, respectively.
Keywords
- Conformational change
- Nuclear magnetic resonance spectroscopy
- Protein phosphorylation
- Protein-protein interaction
- Transactivation domain structure
- Transcription activation
ASJC Scopus subject areas
- Biophysics
- Structural Biology
- Biochemistry
- Molecular Biology
- Genetics
- Cell Biology