ArticleProceedings of the National Academy of Sciences of the United States of America2005
Comparison of the protein-protein interfaces in the p53-DNA crystal structures: towards elucidation of the biological interface.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Deciphering the mechanisms of HPV E6 mutations in the destabilization of E6/E6AP/p53 complex.Biophysical journal · 2022Article
- A novel hotspot and rare somatic mutation p.A138V, at TP53 is associated with poor survival of pancreatic ductal and periampullary adenocarcinoma patients.Molecular medicine (Cambridge, Mass.) · 2020Article
- Conformational stability and dynamics of the cancer-associated isoform Δ133p53β are modulated by p53 peptides and p53-specific DNA.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Transactivation specificity is conserved among p53 family proteins and depends on a response element sequence code.Nucleic acids research · 2013Article
- Crystal structure of the p53 core domain bound to a full consensus site as a self-assembled tetramer.Structure (London, England : 1993) · 2010Article
- Nuance in the double-helix and its role in protein-DNA recognition.Current opinion in structural biology · 2009Review
- Kinase packing defects as drug targets.Drug discovery today · 2007Review
- Human p53 is inhibited by glutathionylation of cysteines present in the proximal DNA-binding domain during oxidative stress.Biochemistry · 2007Article
- Probing potential binding modes of the p53 tetramer to DNA based on the symmetries encoded in p53 response elements.Nucleic acids research · 2007Article
- Sequence analysis of p53 response-elements suggests multiple binding modes of the p53 tetramer to DNA targets.Nucleic acids research · 2007Article
- Crystal structure of SV40 large T-antigen bound to p53: interplay between a viral oncoprotein and a cellular tumor suppressor.Genes & development · 2006Article
- Cooperative fluctuations point to the dimerization interface of p53 core domain.Biophysical journal · 2006Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
p53, the tumor suppressor protein, functions as a dimer of dimers. However, how the tetramer binds to the DNA is still an open question. In the crystal structure, three copies of the p53 monomers (containing chains A, B, and C) were crystallized with the DNA-consensus element. Although the structure provides crucial data on the p53-DNA contacts, the active oligomeric state is unclear because the two dimeric (A-B and B-C) interfaces present in the crystal cannot both exist in the tetramer. Here, we address the question of which of these two dimeric interfaces may be more biologically relevant. We analyze the sequence and structural properties of the p53-p53 dimeric interfaces and carry out extensive molecular dynamics simulations of the crystal structures of the human and mouse p53 dimers. We find that the A-B interface residues are more conserved than those of the B-C. Molecular dynamics simulations show that the A-B interface can provide a stable DNA-binding motif in the dimeric state, unlike B-C. Our results indicate that the interface between chains A-B in the p53-DNA complex constitutes a better candidate for a stable biological interface, whereas the B-C interface is more likely to be due to crystal packing. Thus, they have significant implications toward our understanding of DNA binding by p53 as well as p53-mediated interactions with other proteins.
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