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Record W1942328895 · doi:10.1021/acs.jproteome.5b00574

Identification of <i>Salmonella</i> Typhimurium Deubiquitinase SseL Substrates by Immunoaffinity Enrichment and Quantitative Proteomic Analysis

2015· article· en· W1942328895 on OpenAlexaff
Ernesto Nakayasu, Michael Sydor, Roslyn N. Brown, Ryan Sontag, Tiago J. P. Sobreira, Gordon Slysz, Daniel Humphrys, T. Skarina, Olena Onoprienko, Rosa Di Leo, Brooke L. Deatherage Kaiser, Jie Li, Charles Ansong, Eric D. Cambronne, Richard Smith, Alexei Savchenko, Joshua Adkins

Bibliographic record

VenueJournal of Proteome Research · 2015
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicUbiquitin and proteasome pathways
Canadian institutionsStructural Genomics ConsortiumOntario GenomicsUniversity of Toronto
FundersPacific Northwest National LaboratoryBattelleNational Institute of General Medical SciencesNational Institutes of HealthNational Institute of Allergy and Infectious DiseasesU.S. Department of Energy
KeywordsDeubiquitinating enzymeUbiquitinBiologyEnzymeSalmonellaSalmonella entericaBiochemistryImmunoprecipitationComputational biologyChemistryBacteriaGeneGenetics

Abstract

fetched live from OpenAlex

Ubiquitination is a key protein post-translational modification that regulates many important cellular pathways and whose levels are regulated by equilibrium between the activities of ubiquitin ligases and deubiquitinases. Here, we present a method to identify specific deubiquitinase substrates based on treatment of cell lysates with recombinant enzymes, immunoaffinity purification, and global quantitative proteomic analysis. As a model system to identify substrates, we used a virulence-related deubiquitinase, SseL, secreted by Salmonella enterica serovar Typhimurium into host cells. Using this approach, two SseL substrates were identified in the RAW 264.7 murine macrophage-like cell line, S100A6 and heterogeneous nuclear ribonuclear protein K, in addition to the previously reported K63-linked ubiquitin chains. These substrates were further validated by a combination of enzymatic and binding assays. This method can be used for the systematic identification of substrates of deubiquitinases from other organisms and applied to study their functions in physiology and disease.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame distilled prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.

metaresearch head score (Codex)0.007
metaresearch head score (Gemma)0.001
Version: codex-gemma-dda1882f352aValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Bench or experimental · Consensus signal: Bench or experimental
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.006
Threshold uncertainty score0.462

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0070.001
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.001
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0000.000
Research integrity0.0000.000
Insufficient payload (model declined to judge)0.0000.000

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.061
GPT teacher head0.363
Teacher spread0.302 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one teacher head, not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designBench or experimental
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations14
Published2015
Admission routes1
Has abstractyes

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