Modulation of the Disordered Conformational Ensembles of the p53 Transactivation Domain by Cancer-Associated Mutations
Fig 1
Domain structures of A) p53, and B) CREB-binding protein (CBP).
Also shown in A) include: the sequence of p53-TAD (in bold fonts with phosphorylation sites marked in red), known cancer mutants (in light fonts below the sequence; three additional mutants, P60L/S/Q, are not shown), and its key interaction partners to be studied. Both TAD sub-domains, TAD1 (1–40) and TAD2 (41–61), contain short helices (pα1, pα2) that form upon specific binding to various targets. Four separate CBP domains (colored in grey) can interact with p53-TAD. Abbreviations: TAD: transactivation domain (1–61); P-rich: proline rich region; DBD: DNA-binding domain (102–292); TD: tetramerization domain (325–356); NRD: negative regulatory domain; TAZ1 (340–439) & TAZ2 (1764–1855): cysteine-histidine-rich regions; KIX (586–572), NCBD: nuclear receptor coactivator binding domain (2059–2117).