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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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Overview of the p73 DBD structure. (a) Ribbon representation of the 1.8‐Å crystal structure of the human p73 DBD, highlighting the different secondary structural elements. The remaining portion of the C-terminal TEV cleavage site is colored gray. Bound zinc ions are shown as blue spheres. (b) Multiple sequence alignment of the p53 family DBD generated with Clustal W and visualized with JalView.26 Filled triangles indicate the positions of conserved DNA contact residues. Structure image was generated with PyMOL.
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f0010: Overview of the p73 DBD structure. (a) Ribbon representation of the 1.8‐Å crystal structure of the human p73 DBD, highlighting the different secondary structural elements. The remaining portion of the C-terminal TEV cleavage site is colored gray. Bound zinc ions are shown as blue spheres. (b) Multiple sequence alignment of the p53 family DBD generated with Clustal W and visualized with JalView.26 Filled triangles indicate the positions of conserved DNA contact residues. Structure image was generated with PyMOL.

Mentions: The p73 structure shows a conserved domain architecture, comprising a β-sandwich scaffold consisting of two antiparallel β-sheets (Fig. 1).27 The DNA-binding surface is constructed similarly from the large L2 and L3 loops, the S10 β-strand and a loop–sheet–helix motif that includes the L1 loop, the S2 and S2′ β-strands and the C-terminal H2 α-helix. A conserved zinc ion coordinates the L2 and L3 loops (p73 C194, H197, C258 and C262; Supplementary Fig. S1a) and contributes to the stability of the overall fold. The p73 structure also includes a second metal ion (Supplementary Fig. S1b) trapped at the interface of a crystallographic dimer formed by the H2 helix and the C-terminal His-tag (Supplementary Fig. S2). Here, the coordinating residues include the side chains of C295, C297 and D301 from one monomer and H308 from the second monomer (Supplementary Fig. S2). Both metal ions were confirmed as zinc based on multiwavelength anomalous diffraction data (Supplementary Fig. S3).


Structural basis for ASPP2 recognition by the tumor suppressor p73.

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

Overview of the p73 DBD structure. (a) Ribbon representation of the 1.8‐Å crystal structure of the human p73 DBD, highlighting the different secondary structural elements. The remaining portion of the C-terminal TEV cleavage site is colored gray. Bound zinc ions are shown as blue spheres. (b) Multiple sequence alignment of the p53 family DBD generated with Clustal W and visualized with JalView.26 Filled triangles indicate the positions of conserved DNA contact residues. Structure image was generated with PyMOL.
© Copyright Policy
Related In: Results  -  Collection

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

f0010: Overview of the p73 DBD structure. (a) Ribbon representation of the 1.8‐Å crystal structure of the human p73 DBD, highlighting the different secondary structural elements. The remaining portion of the C-terminal TEV cleavage site is colored gray. Bound zinc ions are shown as blue spheres. (b) Multiple sequence alignment of the p53 family DBD generated with Clustal W and visualized with JalView.26 Filled triangles indicate the positions of conserved DNA contact residues. Structure image was generated with PyMOL.
Mentions: The p73 structure shows a conserved domain architecture, comprising a β-sandwich scaffold consisting of two antiparallel β-sheets (Fig. 1).27 The DNA-binding surface is constructed similarly from the large L2 and L3 loops, the S10 β-strand and a loop–sheet–helix motif that includes the L1 loop, the S2 and S2′ β-strands and the C-terminal H2 α-helix. A conserved zinc ion coordinates the L2 and L3 loops (p73 C194, H197, C258 and C262; Supplementary Fig. S1a) and contributes to the stability of the overall fold. The p73 structure also includes a second metal ion (Supplementary Fig. S1b) trapped at the interface of a crystallographic dimer formed by the H2 helix and the C-terminal His-tag (Supplementary Fig. S2). Here, the coordinating residues include the side chains of C295, C297 and D301 from one monomer and H308 from the second monomer (Supplementary Fig. S2). Both metal ions were confirmed as zinc based on multiwavelength anomalous diffraction data (Supplementary Fig. S3).

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