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Structural basis for ASPP2 recognition by the tumor suppressor p73.

Canning P, von Delft F, Bullock AN - J. Mol. Biol. (2012)

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.

View Article: PubMed Central - PubMed

Affiliation: Structural Genomics Consortium, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford OX3 7DQ, UK.

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Specific packing interactions in the p73–ASPP2 complex. (a) Superposition of the p53 and p73 complexes reveals a significant shift in the position of the n-Src loop, leading to the loss of p73 R268 interaction with ASPP2 D1093 (this side chain was not clearly defined in the electron density). (b) Structural superposition again reveals a shift in the packing of the p73–ASPP2 complex. The L2 loop insertion in p73 induces a subtle change in the position of the H1 helix. Consequently, the loop of the fourth ankyrin repeat in ASPP2 is shifted by ~ 2 Å to avoid steric clashes. Significant sequence changes result in distinct packing interactions in the two complexes.
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f0040: Specific packing interactions in the p73–ASPP2 complex. (a) Superposition of the p53 and p73 complexes reveals a significant shift in the position of the n-Src loop, leading to the loss of p73 R268 interaction with ASPP2 D1093 (this side chain was not clearly defined in the electron density). (b) Structural superposition again reveals a shift in the packing of the p73–ASPP2 complex. The L2 loop insertion in p73 induces a subtle change in the position of the H1 helix. Consequently, the loop of the fourth ankyrin repeat in ASPP2 is shifted by ~ 2 Å to avoid steric clashes. Significant sequence changes result in distinct packing interactions in the two complexes.

Mentions: Overall, the p73–ASPP2 structure is highly conserved with the p53 complex but exhibits a shift in the ASPP2 position to better accommodate the variant p73 L2 loop (Fig. 6). As a result, the contact surface area of the p53–ASPP2 structure (753 Å2) is slightly greater than that of the p73–ASPP2 complex, which varies across the noncrystallographic‐symmetry‐related molecules from 672 to 742 Å2. The binding of both proteins is directed primarily by the L3 loop interaction with the ASPP2 SH3 domain (Fig. 7a) but supported by further L2 loop contact with the fourth ankyrin repeat (Fig. 7b).


Structural basis for ASPP2 recognition by the tumor suppressor p73.

Canning P, von Delft F, Bullock AN - J. Mol. Biol. (2012)

Specific packing interactions in the p73–ASPP2 complex. (a) Superposition of the p53 and p73 complexes reveals a significant shift in the position of the n-Src loop, leading to the loss of p73 R268 interaction with ASPP2 D1093 (this side chain was not clearly defined in the electron density). (b) Structural superposition again reveals a shift in the packing of the p73–ASPP2 complex. The L2 loop insertion in p73 induces a subtle change in the position of the H1 helix. Consequently, the loop of the fourth ankyrin repeat in ASPP2 is shifted by ~ 2 Å to avoid steric clashes. Significant sequence changes result in distinct packing interactions in the two complexes.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC3472557&req=5

f0040: Specific packing interactions in the p73–ASPP2 complex. (a) Superposition of the p53 and p73 complexes reveals a significant shift in the position of the n-Src loop, leading to the loss of p73 R268 interaction with ASPP2 D1093 (this side chain was not clearly defined in the electron density). (b) Structural superposition again reveals a shift in the packing of the p73–ASPP2 complex. The L2 loop insertion in p73 induces a subtle change in the position of the H1 helix. Consequently, the loop of the fourth ankyrin repeat in ASPP2 is shifted by ~ 2 Å to avoid steric clashes. Significant sequence changes result in distinct packing interactions in the two complexes.
Mentions: Overall, the p73–ASPP2 structure is highly conserved with the p53 complex but exhibits a shift in the ASPP2 position to better accommodate the variant p73 L2 loop (Fig. 6). As a result, the contact surface area of the p53–ASPP2 structure (753 Å2) is slightly greater than that of the p73–ASPP2 complex, which varies across the noncrystallographic‐symmetry‐related molecules from 672 to 742 Å2. The binding of both proteins is directed primarily by the L3 loop interaction with the ASPP2 SH3 domain (Fig. 7a) but supported by further L2 loop contact with the fourth ankyrin repeat (Fig. 7b).

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.

View Article: PubMed Central - PubMed

Affiliation: Structural Genomics Consortium, University of Oxford, Old Road Campus, Roosevelt Drive, Oxford OX3 7DQ, UK.

Show MeSH
Related in: MedlinePlus