Open AccessStructure of the Taz2 domain of p300: insights into ligand binding
Author(s) -
Miller Maria,
Dauter Zbigniew,
Cherry Scott,
Tropea Joseph E.,
Wlodawer Alexander
Publication year - 2009
Publication title -
acta crystallographica section d
Language(s) - English
Resource type - Journals
ISSN - 1399-0047
DOI - 10.1107/s0907444909040153
Subject(s) - transactivation , helix bundle , binding site , crystallography , crystal structure , chemistry , biophysics , protein structure , zinc finger , computational biology , transcription factor , biology , gene , biochemistry
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.