2RUK: Solution structure of the complex between p53 transactivation domain 2 and TFIIH p62 PH domain

The transactivation domain (TAD) of tumor suppressor p53 has homologous subdomains, TAD1 and TAD2. Both are intrinsically disordered in their free states, but all structures of TAD1 and TAD2 bound to their target proteins have demonstrated use of an amphipathic alpha-helix, suggesting that the binding-coupled helix folding mechanism of TAD1 and TAD2 is essential. Although phosphorylation of TAD is important to switch the function of p53, bound structures of phosphorylated TAD1 and TAD2 have not been determined. 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. This string-like binding mode of TAD2 seems to be independent of its phosphorylation in spite of enhanced binding activity upon phosphorylation. This is in contrast to the amphipathic helical binding mode of the unphosphorylated TAD2 to the yeast tfb1 PH domain and demonstrates that the p53 TAD2 has much higher conformational malleability than previously appreciated.
PDB ID: 2RUKDownload
MMDB ID: 123751
PDB Deposition Date: 2014/9/24
Updated in MMDB: 2014/10
Experimental Method:
solution nmr
Source Organism:
Similar Structures:
Biological Unit for 2RUK: dimeric; determined by author
Molecular Components in 2RUK
Label Count Molecule
Proteins (2 molecules)
Cellular Tumor Antigen P53(Gene symbol: TP53)
Molecule annotation
General Transcription Factor IIH Subunit 1(Gene symbol: GTF2H1)
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB