Evidence map›Paper›PMID 27604871›Full record

ArticleNucleic acids research2016

DNA-binding protects p53 from interactions with cofactors involved in transcription-independent functions.

Matteo Lambrughi, Luca De Gioia, Francesco Luigi Gervasio, Kresten Lindorff-Larsen, Ruth Nussinov, Chiara Urani, Maurizio Bruschi, Elena Papaleo

Open access · goldAbstract read
In one paragraph

Article in Nucleic acids research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
3.3field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

24 citing papers in PubMed, 44 citations in OpenAlex.

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  18. Computational Structural Biology ofFrontiers in oncology · 2018
    Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 4 institutions in 5 countries.

Matteo LambrughiComputational Biology Laboratory, Unit of Statistics, Bioinformatics and Registry, Strandboulevarden 49, 2100, Copenhagen, Denmark.
Luca De GioiaDepartment of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126, Milan, Italy.
Francesco Luigi GervasioDepartment of Chemistry and Institute of Structural and Molecular Biology, University College London, London WC1H 0AJ, UK.
Kresten Lindorff-LarsenStructural Biology and NMR Laboratory, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
Ruth NussinovCancer and Inflammation Program, Leidos Biomedical Research Inc., Frederick National laboratory, National Cancer Institute, Frederick, MD 21702, USA.
Chiara UraniDepartment of Earth and Environmental Sciences, University of Milano-Bicocca, Piazza della Scienza 1, 20126, Milan, Italy.
Maurizio BruschiDepartment of Earth and Environmental Sciences, University of Milano-Bicocca, Piazza della Scienza 1, 20126, Milan, Italy.
Elena PapaleoComputational Biology Laboratory, Unit of Statistics, Bioinformatics and Registry, Strandboulevarden 49, 2100, Copenhagen, Denmark elenap@cancer.dk.ORCID http://orcid.org/0000-0002-7376-5894
University of Copenhagen · DKUniversity of Milano-Bicocca · ITInstitute of Structural and Molecular Biology · GBLeidos (United States) · US

Funding

Biomolecular Recognition and Binding MechanismsZIABC010441 · NCI · DIVISION OF BASIC SCIENCES - NCI · PI NUSSINOV, RUTH · 2009 to 2025
$9.4M
CCR NIH HHS HHSN261200800001CNCI NIH HHS HHSN261200800001E
6 · The paper itself

Abstract

Binding-induced conformational changes of a protein at regions distant from the binding site may play crucial roles in protein function and regulation. The p53 tumour suppressor is an example of such an allosterically regulated protein. Little is known, however, about how DNA binding can affect distal sites for transcription factors. Furthermore, the molecular details of how a local perturbation is transmitted through a protein structure are generally elusive and occur on timescales hard to explore by simulations. Thus, we employed state-of-the-art enhanced sampling atomistic simulations to unveil DNA-induced effects on p53 structure and dynamics that modulate the recruitment of cofactors and the impact of phosphorylation at Ser215. We show that DNA interaction promotes a conformational change in a region 3 nm away from the DNA binding site. Specifically, binding to DNA increases the population of an occluded minor state at this distal site by more than 4-fold, whereas phosphorylation traps the protein in its major state. In the minor conformation, the interface of p53 that binds biological partners related to p53 transcription-independent functions is not accessible. Significantly, our study reveals a mechanism of DNA-mediated protection of p53 from interactions with partners involved in the p53 transcription-independent signalling. This also suggests that conformational dynamics is tightly related to p53 signalling.

Indexed as

Transcription, GeneticBinding SitesCarrier ProteinsDNAHydrogen BondingMagnetic Resonance SpectroscopyModels, MolecularMolecular ConformationProtein BindingProtein Interaction Domains and MotifsProtein Interaction MappingTumor Suppressor Protein p53Carrier ProteinsDNATumor Suppressor Protein p53

Identifiers

PMID27604871
PMCPMC5100575
OpenAlexW2513997651

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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Registered trials

None linked

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.