ArticleThe EMBO journal2011
An induced fit mechanism regulates p53 DNA binding kinetics to confer sequence specificity.
Article in The EMBO journal, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 1 of them a synthesis that pooled it.
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Who cites it
65 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Targeting p53 pathways: mechanisms, structures, and advances in therapy.Signal transduction and targeted therapy · 2023Pooled it
- Evaluation of non-canonical p53 functions in DNA replication and recombination for variant classification.Cell death & disease · 2026Article
- Lung cancer-enriched p53 mutants occupy canonical p53 target genes without activating transcription, revealing a distinct loss-of-function behavior.bioRxiv : the preprint server for biology · 2026Article
- Hollow condensates emerge from gelation-induced spinodal decomposition.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
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- Article
- DNA-binding proteins from MBD through ZF to BEN: recognition of cytosine methylation status by one arginine with two conformations.Nucleic acids research · 2024Article
- Geometric deep learning of protein-DNA binding specificity.Nature methods · 2024Article
- Multiscale simulations reveal the driving forces of p53C phase separation accelerated by oncogenic mutations.Chemical science · 2024Article
- Navigating the complexity of p53-DNA binding: implications for cancer therapy.Biophysical reviews · 2024Review
- Phage libraries screening on P53: Yield improvement by zinc and a new parasites-integrating analysis.PloS one · 2024Article
- Accurate prediction of protein-nucleic acid complexes using RoseTTAFoldNA.Nature methods · 2024Article
- Single molecule studies characterize the kinetic mechanism of tetrameric p53 binding to different native response elements.PloS one · 2023Article
- Mapping Interactions of the Intrinsically Disordered C-Terminal Regions of Tetrameric p53 by Segmental Isotope Labeling and NMR.Biochemistry · 2022Article
- Article
- Insights into Allosteric Mechanisms of the Lung-Enriched p53 Mutants V157F and R158L.International journal of molecular sciences · 2022Article
- Structural basis of reactivation of oncogenic p53 mutants by a small molecule: methylene quinuclidinone (MQ).Nature communications · 2021Article
- Dying to Survive-The p53 Paradox.Cancers · 2021Review
- Association between Predicted Effects ofInternational journal of molecular sciences · 2021Article
- Decreased GLUT2 and glucose uptake contribute to insulin secretion defects in MODY3/HNF1A hiPSC-derived mutant β cells.Nature communications · 2021Article
5 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The p53 tumour suppressor gene, the most frequently mutated gene in human cancer, encodes a transcription factor that contains sequence-specific DNA binding and homo-tetramerization domains. Interestingly, the affinities of p53 for specific and non-specific DNA sites differ by only one order of magnitude, making it hard to understand how this protein recognizes its specific DNA targets in vivo. We describe here the structure of a p53 polypeptide containing both the DNA binding and oligomerization domains in complex with DNA. The structure reveals that sequence-specific DNA binding proceeds via an induced fit mechanism that involves a conformational switch in loop L1 of the p53 DNA binding domain. Analysis of loop L1 mutants demonstrated that the conformational switch allows DNA binding off-rates to be regulated independently of affinities. These results may explain the universal prevalence of conformational switching in sequence-specific DNA binding proteins and suggest that proteins like p53 rely more on differences in binding off-rates, than on differences in affinities, to recognize their specific DNA sites.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.