Related Experiment Videos
Solution structure of the TAZ2 (CH3) domain of the transcriptional adaptor protein CBP
R N De Guzman1, H Y Liu, M Martinez-Yamout
1Department of Molecular Biology and Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Rd, La Jolla, CA 92037, USA.
Abstract:
The TAZ2 (CH3) domain of the transcriptional adapter protein CBP has been implicated in direct functional interactions with numerous cellular transcription factors and viral oncoproteins. The solution structure of the TAZ2 domain of murine CBP has been determined by nuclear magnetic resonance (NMR). The protein adopts a novel helical fold stabilized by three zinc ions, each of which is bound to one histidine and three cysteine ligands in HCCC-type motifs. Each zinc-binding site is formed from the carboxy terminus of an alpha-helix, a short loop, and the amino terminus of the next alpha-helix. A peptide derived from the N-terminal transactivation domain of p53 binds specifically to one face of the TAZ2 domain. The close similarities between the TAZ2 and TAZ1 (CH1 domain of CBP/p300) sequences suggest that both domains will adopt similar three-dimensional structures.
Insights
The TAZ2 domain of CBP, crucial for protein interactions, was structurally analyzed using NMR. Its novel helical fold, stabilized by zinc ions, binds to p53 peptides.
Area of Science:
- Biochemistry
- Structural Biology
- Molecular Biology
Background:
- The CBP TAZ2 (CH3) domain interacts with transcription factors and viral oncoproteins.
- Understanding TAZ2 structure is key to deciphering CBP's regulatory functions.
Purpose of the Study:
- To determine the solution structure of the murine CBP TAZ2 domain.
- To investigate the structural basis for TAZ2 interactions, including with p53.
Main Methods:
- Nuclear Magnetic Resonance (NMR) spectroscopy was used to determine the solution structure.
- Structural analysis of the TAZ2 domain and its interaction with a p53-derived peptide.
Main Results:
- The TAZ2 domain adopts a novel helical fold stabilized by three zinc ions.
- Each zinc ion is coordinated by histidine and cysteine ligands in HCCC motifs.
- A p53 peptide specifically binds to one face of the TAZ2 domain.
Conclusions:
- The determined structure provides insights into the CBP TAZ2 domain's fold and zinc-binding sites.
- The specific binding of p53 suggests a direct interaction mechanism.
- Structural similarities between TAZ1 and TAZ2 domains imply conserved structural motifs within CBP/p300 family proteins.