P53-DNA Recognition: Difference between revisions
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==Introduction and Biological Role of the Tumor Suppressor p53== | ==Introduction and Biological Role of the Tumor Suppressor p53== | ||
[[Image:p53-intro.jpg|thumb|left|300px|Figure 1: Crystal structure of a p53 DBD tetramer-DNA complex; [http://www.proteopedia.org/wiki/index.php/3kz8 PDB ID# 3KZ8]<ref name='kitayner'>Kitayner M, Rozenberg H, Rohs R, Suad O, Rabinovich D, Honig B, Shakked Z. Diversity in DNA recognition by p53 revealed by crystal structures with Hoogsteen base pairs. Nat Struct Mol Biol. 2010;17(4):423-9.</ref>.]] | [[Image:p53-intro.jpg|thumb|left|300px|Figure 1: Crystal structure of a p53 DBD tetramer-DNA complex; [http://www.proteopedia.org/wiki/index.php/3kz8 PDB ID# 3KZ8]<ref name='kitayner'>Kitayner M, Rozenberg H, Rohs R, Suad O, Rabinovich D, Honig B, Shakked Z. Diversity in DNA recognition by p53 revealed by crystal structures with Hoogsteen base pairs. Nat Struct Mol Biol. 2010;17(4):423-9. [http://www.ncbi.nlm.nih.gov/pubmed/20364130 PMID:20364130].</ref>.]] | ||
[[Image:consensus.jpg|thumb|right|250px|Figure 2: p53 consensus site; R= A or G, Y= C or T, and W=A or T.]] | [[Image:consensus.jpg|thumb|right|250px|Figure 2: p53 consensus site; R= A or G, Y= C or T, and W=A or T.]] | ||
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As for p53-DNA recognition, Hoogsteen base pairs are not present in the complex with a different DNA sequence <ref name="chen">Chen Y, Dey R, Chen L. Crystal structure of the p53 core domain bound to a full consensus site as a self-assembled tetramer. Structure. 2010;18(2):246-56.</ref> but the DNA undergoes a different deformation not observed in the complex with Hoogsteen base pairing. Since transient Hoogsteen base pairs have been detected in naked DNA with preferences for CA and TA dincucleotides<ref name="hashimi">Nikolova EN, Kim E, Wise AA, O'Brien PJ, Andricioaei I, Al-Hashimi HM. Transient Hoogsteen base pairs in canonical duplex DNA. Nature. 2011;470(7335):498-502.</ref>, the observation of the base pairing variant in p53-DNA complexes indicates a sequence-speific feature of the response element either recognized or stabilized by p53. | As for p53-DNA recognition, Hoogsteen base pairs are not present in the complex with a different DNA sequence <ref name="chen">Chen Y, Dey R, Chen L. Crystal structure of the p53 core domain bound to a full consensus site as a self-assembled tetramer. Structure. 2010;18(2):246-56.</ref> but the DNA undergoes a different deformation not observed in the complex with Hoogsteen base pairing. Since transient Hoogsteen base pairs have been detected in naked DNA with preferences for CA and TA dincucleotides<ref name="hashimi">Nikolova EN, Kim E, Wise AA, O'Brien PJ, Andricioaei I, Al-Hashimi HM. Transient Hoogsteen base pairs in canonical duplex DNA. Nature. 2011;470(7335):498-502.</ref>, the observation of the base pairing variant in p53-DNA complexes indicates a sequence-speific feature of the response element either recognized or stabilized by p53. | ||
A more general discussion of structural origins of binding specificity in protein-DNA recognition has been published along with a suggestion for a new '''classification of protein-DNA readout modes''' that goes beyond the historical description of direct and indirect readout<ref name="annualreview">Rohs R, Jin X, West SM, Joshi R, Honig B, Mann RS. Origins of specificity in protein-DNA recognition. Annu Rev Biochem. 2010;79:233-69. [http://www.ncbi.nlm.nih.gov/pubmed/20334529 PMID:20334529]</ref>.<br/> | A more general discussion of structural origins of binding specificity in protein-DNA recognition has been published along with a suggestion for a new '''classification of protein-DNA readout modes''' that goes beyond the historical description of direct and indirect readout<ref name="annualreview">Rohs R, Jin X, West SM, Joshi R, Honig B, Mann RS. Origins of specificity in protein-DNA recognition. Annu Rev Biochem. 2010;79:233-69. [http://www.ncbi.nlm.nih.gov/pubmed/20334529 PMID:20334529].</ref>.<br/> | ||
=Acknowledgements= | =Acknowledgements= | ||