2RUK

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

Summary for 2RUK

• Entry DOI: 10.2210/pdb2ruk/pdb
• NMR Information: BMRB: 11578
• Descriptor: Cellular tumor antigen p53, General transcription factor IIH subunit 1 (2 entities in total)
• Functional Keywords: antitumor protein, general transcription factor, ph domain, transcription
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm. Isoform 1: Nucleus. Isoform 2: Nucleus. Isoform 3: Nucleus. Isoform 4: Nucleus. Isoform 7: Nucleus. Isoform 8: Nucleus. Isoform 9: Cytoplasm: P04637; Nucleus: P32780
• Total number of polymer chains: 2
• Total formula weight: 15175.05

Authors

Okuda, M.,Nishimura, Y. (deposition date: 2014-09-24, release date: 2014-10-15, Last modification date: 2024-10-16)

Primary citation

Okuda, M.,Nishimura, Y.
Extended string binding mode of the phosphorylated transactivation domain of tumor suppressor p53.
J.Am.Chem.Soc., 136:14143-14152, 2014

PubMed Abstract: 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 α-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.

PubMed: 25216154
DOI: 10.1021/ja506351f

Experimental method

SOLUTION NMR