ArticleProceedings of the National Academy of Sciences of the United States of America2011
Solution X-ray scattering combined with computational modeling reveals multiple conformations of covalently bound ubiquitin on PCNA.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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.
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.
Who cites it
40 citing papers in PubMed, 62 citations in OpenAlex.
- A High-Throughput Small-Angle X-ray Scattering Assay to Determine the Conformational Change of Plasminogen.International journal of molecular sciences · 2023Article
- Combining small angle X-ray scattering (SAXS) with protein structure predictions to characterize conformations in solution.Methods in enzymology · 2023Article
- Unorthodox PCNA Binding by Chromatin Assembly Factor 1.International journal of molecular sciences · 2022Article
- Universally Accessible Structural Data on Macromolecular Conformation, Assembly, and Dynamics by Small Angle X-Ray Scattering for DNA Repair Insights.Methods in molecular biology (Clifton, N.J.) · 2022Article
- Cryo-EM structure of human Pol κ bound to DNA and mono-ubiquitylated PCNA.Nature communications · 2021Article
- Function and Molecular Mechanism of the DNA Damage Response in Immunity and Cancer Immunotherapy.Frontiers in immunology · 2021Review
- Quantitative comparison between sub-millisecond time resolution single-molecule FRET measurements and 10-second molecular simulations of a biosensor protein.PLoS computational biology · 2020Article
- Dual role of a GTPase conformational switch for membrane fusion by mitofusin ubiquitylation.Life science alliance · 2020Article
- Small angle X-ray scattering-assisted protein structure prediction in CASP13 and emergence of solution structure differences.Proteins · 2019Article
- Evolving SAXS versatility: solution X-ray scattering for macromolecular architecture, functional landscapes, and integrative structural biology.Current opinion in structural biology · 2019Review
- Conformational Flexibility of Ubiquitin-Modified and SUMO-Modified PCNA Shown by Full-Ensemble Hybrid Methods.Journal of molecular biology · 2018Article
- Review
- Eukaryotic Translesion DNA Synthesis on the Leading and Lagging Strands: Unique Detours around the Same Obstacle.Chemical reviews · 2017Review
- Translesion DNA polymerases in eukaryotes: what makes them tick?Critical reviews in biochemistry and molecular biology · 2017Review
- Disentangling polydispersity in the PCNA-p15PAF complex, a disordered, transient and multivalent macromolecular assembly.Nucleic acids research · 2017Article
- What Combined Measurements From Structures and Imaging Tell Us About DNA Damage Responses.Methods in enzymology · 2017Review
- Article
- Secondary Interaction Interfaces with PCNA Control Conformational Switching of DNA Polymerase PolB from Polymerization to Editing.The journal of physical chemistry. B · 2016Article
- Non-degradative Ubiquitination of Protein Kinases.PLoS computational biology · 2016Article
- Identifying and Visualizing Macromolecular Flexibility in Structural Biology.Frontiers in molecular biosciences · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 5 institutions in 1 country.
Funding
Abstract
PCNA ubiquitination in response to DNA damage leads to the recruitment of specialized translesion polymerases to the damage locus. This constitutes one of the initial steps in translesion synthesis (TLS)--a critical pathway for cell survival and for maintenance of genome stability. The recent crystal structure of ubiquitinated PCNA (Ub-PCNA) sheds light on the mode of association between the two proteins but also revealed that paradoxically, the ubiquitin surface engaged in PCNA interactions was the same as the surface implicated in translesion polymerase binding. This finding implied a degree of flexibility inherent in the Ub-PCNA complex that would allow it to transition into a conformation competent to bind the TLS polymerase. To address the issue of segmental flexibility, we combined multiscale computational modeling and small angle X-ray scattering. This combined strategy revealed alternative positions for ubiquitin to reside on the surface of the PCNA homotrimer, distinct from the position identified in the crystal structure. Two mutations originally identified in genetic screens and known to interfere with TLS are positioned directly beneath the bound ubiquitin in the alternative models. These computationally derived positions, in an ensemble with the crystallographic and flexible positions, provided the best fit to the solution scattering, indicating that ubiquitin dynamically associated with PCNA and is capable of transitioning between a few discrete sites on the PCNA surface. The finding of new docking sites and the positional equilibrium of PCNA-Ub occurring in solution provide unexpected insight into previously unexplained biological observations.
Indexed as
Identifiers
What OpenQuestion holds
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.