IndraLab

"Although phosphorylation of TAD is important to switch the function of p53, bound structures of phosphorylated TAD1 and TAD2 have not been determined."

"Intriguingly, the binding affinity of hTFIIEα 336−439 to p62 PH-D is much stronger than unphosphorylated p53 TAD2 and is comparable to doubly phosphorylated TAD2."

"Here, we reveal the recognition mechanism of the phosphorylated TAD2 bound to a pleckstrin homology (PH) domain from human TFIIH subunit p62 in an extended string-like conformation."

"In a previous study, we determined the structure of the complex between the p53-TAD2 peptide (residues 41–62), doubly phosphorylated on Ser46 and Thr55, and p62-PH of TFIIH using NMR and revealed that phosphorylated Ser46 and Thr55 make electrostatic contacts with K18/K19 and K54, respectively, of p62-PH ( xref ). xref (Note that, to avoid confusion, residues of p53 and XPC are represented by three-letter code and those of p62 are represented by one-letter code in this paper.) We also quantitatively examined the effects of phosphorylation of p53-TAD2 on binding to p62-PH by using isothermal titration calorimetry (ITC) and NMR."

"Although phosphorylation of TAD is important to switch the function of p53, bound structures of phosphorylated TAD1 and TAD2 have not been determined."

"In the native state, the phosphorylated TAD2 forms an elongated string-like conformation with tryptophan (Trp53) buried inside deeply."

"Here, we reveal the recognition mechanism of the phosphorylated TAD2 bound to a pleckstrin homology (PH) domain from human TFIIH subunit p62 in an extended string-like conformation."

"Both TAD1 and TAD2 of p53 are extensively phosphorylated on multiple residues in response to carcinogenic stress xref ."

"In contrast, phosphorylation of Ser46 at the p53 TAD2 domain by c-Jun NH2-terminal kinase 2α2 (JNK2α2) exerts a weaker influence on the binding affinity, whereas phosphorylation of Ser376 and Ser378 at the C-terminus of p53 by protein kinase C (PKC) appears to have little effect."

"Phosphorylation in TAD2, therefore, does not affect binding of this domain of p53 to Taz2."