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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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Related in: MedlinePlus

Conservation and flexibility of the DNA contact surface. (a) Superposition of the free p53 (orange) and p73 (green) structures showing conserved DNA contact residues as sticks. The side chains of p73 K138 and R268 were not visible in the electron density and were not built. A broken line indicates the disordered segment of the p73 L3 loop (G265–N267). An outline of the p73 surface is displayed in gray. (b) The structures of p53 and p73 are shown in the same orientation and colored by crystallographic B‐factors according to the scale shown.
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f0020: Conservation and flexibility of the DNA contact surface. (a) Superposition of the free p53 (orange) and p73 (green) structures showing conserved DNA contact residues as sticks. The side chains of p73 K138 and R268 were not visible in the electron density and were not built. A broken line indicates the disordered segment of the p73 L3 loop (G265–N267). An outline of the p73 surface is displayed in gray. (b) The structures of p53 and p73 are shown in the same orientation and colored by crystallographic B‐factors according to the scale shown.

Mentions: DNA contact residues in p53 are strictly conserved in p73 (Fig. 3a). The side-chain conformations of p73 K138 and R268 were not defined in the electron density map, suggesting some disorder of these regions in the absence of DNA. The crystallographic B‐factors in p73 are indeed higher in the L1 and L3 loops (Fig. 3b). The conformations of the other flexible arginine or lysine side chains also vary between the unbound p53 and p73 structures, while p73 R293 adopts two distinct conformations. B-factors are lowest around the core β-sandwich, whereas the N‐ and C-termini of both p53 and p73 exhibit higher B‐factors and appear more flexible (Fig. 3b).


Structural basis for ASPP2 recognition by the tumor suppressor p73.

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

Conservation and flexibility of the DNA contact surface. (a) Superposition of the free p53 (orange) and p73 (green) structures showing conserved DNA contact residues as sticks. The side chains of p73 K138 and R268 were not visible in the electron density and were not built. A broken line indicates the disordered segment of the p73 L3 loop (G265–N267). An outline of the p73 surface is displayed in gray. (b) The structures of p53 and p73 are shown in the same orientation and colored by crystallographic B‐factors according to the scale shown.
© Copyright Policy
Related In: Results  -  Collection

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

f0020: Conservation and flexibility of the DNA contact surface. (a) Superposition of the free p53 (orange) and p73 (green) structures showing conserved DNA contact residues as sticks. The side chains of p73 K138 and R268 were not visible in the electron density and were not built. A broken line indicates the disordered segment of the p73 L3 loop (G265–N267). An outline of the p73 surface is displayed in gray. (b) The structures of p53 and p73 are shown in the same orientation and colored by crystallographic B‐factors according to the scale shown.
Mentions: DNA contact residues in p53 are strictly conserved in p73 (Fig. 3a). The side-chain conformations of p73 K138 and R268 were not defined in the electron density map, suggesting some disorder of these regions in the absence of DNA. The crystallographic B‐factors in p73 are indeed higher in the L1 and L3 loops (Fig. 3b). The conformations of the other flexible arginine or lysine side chains also vary between the unbound p53 and p73 structures, while p73 R293 adopts two distinct conformations. B-factors are lowest around the core β-sandwich, whereas the N‐ and C-termini of both p53 and p73 exhibit higher B‐factors and appear more flexible (Fig. 3b).

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