Structural basis for p300 Taz2-p53 TAD1 binding and modulation by phosphorylation.
Coactivators CREB-binding protein and p300 play important roles in mediating the transcriptional activity of p53. Until now, however, no detailed structural information has been available on how any of the domains of p300 interact with p53. Here, we report the NMR structure of the complex of the Taz2 (C/H3) domain of p300 and the N-terminal transactivation domain of p53. In the complex, p53 forms a short alpha helix and interacts with the Taz2 domain through an extended surface. Mutational analyses demonstrate the importance of hydrophobic residues for complex stabilization. Additionally, they suggest that the increased affinity of Taz2 for p53(1-39) phosphorylated at Thr(18) is due in part to electrostatic interactions of the phosphate with neighboring arginine residues in Taz2. Thermodynamic experiments revealed the importance of hydrophobic interactions in the complex of Taz2 with p53 phosphorylated at Ser(15) and Thr(18).
Feng
Hanqiao
H
Laboratory of Biochemistry and Molecular Biology, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
Jenkins
Lisa M Miller
LM
Durell
Stewart R
SR
Hayashi
Ryo
R
Mazur
Sharlyn J
SJ
Cherry
Scott
S
Tropea
Joseph E
JE
Miller
Maria
M
Wlodawer
Alexander
A
Appella
Ettore
E
Bai
Yawen
Y
D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D010766:Phosphorylation / Q000502:physiology; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping; D011494:Protein Kinases / Q000378:metabolism* / Q000502:physiology; D020836:Protein Structure, Quaternary; D012694:Serine / Q000737:chemistry / Q000378:metabolism; D013816:Thermodynamics; D013912:Threonine / Q000737:chemistry / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry* / Q000378:metabolism*; D050880:p300-CBP Transcription Factors / Q000737:chemistry* / Q000378:metabolism*
D016159:Tumor Suppressor Protein p53; D013912:Threonine; D012694:Serine; D050880:p300-CBP Transcription Factors; D011494:Protein Kinases