Structural background of p53-ASPP PPI.

(A) Domain organizations of p53 and ASPP proteins. p53’s DBD and ASPP’s ANK-SH3 are folded domains whereas the remaining sequences are intrinsically disordered. (B) Crystal structures of ASPP2-p53 complex (PDB 1YCS [5]) and iASPP-p53 complex (PDB 6RZ3 [6]). Solution NMR studies [4] also suggest a iASPP-p53 binding mode that is different from PDB 6RZ3. (C) In this study, we combined all-atom and coarse-grained (CG) MDs plus free energy calculations to explore the binding mechanisms between three p53 constructs (p53DBD p53P-DBD and p53P-DBD-L) and the ANK-SH3 domains of ASPP2/iASPP.