Key properties of three IDP complexes.

Abbreviations: ACTR: the activation domain of p160 steroid receptor co-activator; HIF-1α: hypoxia-inducible factor 1 α subunit; NCBD: the nuclear-receptor co-activator binding domain of CREB binding protein (CBP); p53-TAD1: the transactivation domain 1 of tumor suppressor p53; TAZ1/2: the TAZ domains of CBP. The sequences of all IDPs involved (highlighted in bond fonts) are provided in the Supporting Information. Text S1.

The experimental K_D values were measured at 308 K for p53-TAD1/TAZ2, 298 K for HIF-1α/TAZ1, and 304 K for NCBD/ACTR. Note that K_D only weakly depends on temperature for p53-TAD1/TAZ2 (doubled when the temperature is increased from 288K to 308K [77]).

Numbers of charged residues and the net charges (in parentheses) of the IDP, its binding site, and the vicinity of the binding site. Residues at the IDP binding interface are identified as those with greater than 1.0 Ų solvent accessible surface area changes upon complex formation. Surface residues are identified as those with >5% solvent accessibility. All surface residues within 15 Å Cα-Cα distance from the bound IDP but not directly involved in intermolecular contacts are considered to be within the vicinity of the IDP binding site.

Estimated based on the association rate constant of p53-TAD2/TAZ2 (∼10¹⁰ M⁻¹s⁻¹[38]), assuming that TAD1 and TAD2 have similar off rates. TAD2 binds to the TAZ2 primary site with K_D ∼32 nM [38], about two orders of magnitude stronger than TAD1.