Structural basis for ASPP2 recognition by the tumor suppressor p73.
Bottom Line: The loop in p73 is changed by a two-residue insertion that also induces repacking around the site of the p53 mutational hotspot R175.Importantly, the binding of ASPP2 is preserved by conformational changes in both the ankyrin repeat and SH3 domains.These results further highlight the structural variation that impacts p53 family interactions within the p53 interactome.
Affiliation: Structural Genomics Consortium, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford OX3 7DQ, UK.Show MeSH
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Mentions: Superposition of the p53 and p73 domains reveals a high degree of structural similarity (Fig. 2a). The overall Cα root-mean-square deviation (RMSD) between the two structures is 1.7 Å over 191 atoms, consistent with their high sequence conservation (61% identity, Fig. 1b). However, local regions of structural deviation are apparent when the RMSD values are examined across the different secondary‐structure elements (Fig. 2a). As expected, the lowest RMSD values lie in the core β-sandwich, whereas more significant deviation occurs across the DNA binding surface. Both proteins show a strongly electropositive surface potential across the DNA contact surface but more variable charge in the L2 loop, which mediates protein–protein interactions (Fig. 2b).
Affiliation: Structural Genomics Consortium, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford OX3 7DQ, UK.