CBP and its paralog p300 are histone acetyl transferases that regulate gene
expression by interacting with multiple transcription factors via specialized
domains. The structure of a segment of human p300 protein (residues 1723-1836)
corresponding to the extended zinc-binding Taz2 domain has been investigated.
The crystal structure was solved by the SAD approach utilizing the anomalous
diffraction signal of the bound Zn ions. The structure comprises an atypical
helical bundle stabilized by three Zn ions and closely resembles the solution
structures determined previously for shorter peptides. Residues 1813-1834 from
the current construct form a helical extension of the C-terminal helix and make
extensive crystal-contact interactions with the peptide-binding site of Taz2,
providing additional insights into the mechanism of the recognition of diverse
transactivation domains (TADs) by Taz2. On the basis of these results and
molecular modeling, a hypothetical model of the binding of phosphorylated p53
TAD1 to Taz2 has been proposed.
