MétaCan
Menu
Back to cohort
Record W2949033967 · doi:10.1038/s41467-019-10577-3

Inhibition of CRISPR-Cas9 ribonucleoprotein complex assembly by anti-CRISPR AcrIIC2

2019· article· en· W2949033967 on OpenAlex
Annoj Thavalingam, Zhi Cheng, Bianca Garcı́a, Xue Huang, Megha Shah, Wei Sun, Min Wang, Lucas B. Harrington, Sungwon Hwang, Yurima Hidalgo-Reyes, Erik J. Sontheimer, Jennifer A. Doudna, Alan R. Davidson, Trevor F. Moraes, Yanli Wang, Karen L. Maxwell

Why this work is in the frame

A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.

affAt least one author lists a Canadian institution in the pinned OpenAlex snapshot.
fundA Canadian funder is recorded on the work.

Bibliographic record

VenueNature Communications · 2019
Typearticle
Languageen
FieldBiochemistry, Genetics and Molecular Biology
TopicCRISPR and Genetic Engineering
Canadian institutionsUniversity of Toronto
FundersNational Institute of General Medical SciencesChinese Academy of SciencesNational Natural Science Foundation of China-Yunnan Joint FundCanadian Light SourceNatural Sciences and Engineering Research Council of CanadaCanadian Institutes of Health ResearchNational Natural Science Foundation of ChinaNational Institutes of HealthGovernment of CanadaSalt Science Research FoundationMinistry of Science and Technology of the People's Republic of ChinaFoundation for the National Institutes of Health
KeywordsCRISPRRibonucleoproteinGenome editingCas9Trans-activating crRNAComputational biologyBiologyGeneticsRNAGene

Abstract

fetched live from OpenAlex

Abstract CRISPR-Cas adaptive immune systems function to protect bacteria from invasion by foreign genetic elements. The CRISPR-Cas9 system has been widely adopted as a powerful genome-editing tool, and phage-encoded inhibitors, known as anti-CRISPRs, offer a means of regulating its activity. Here, we report the crystal structures of anti-CRISPR protein AcrIIC2 Nme alone and in complex with Nme1Cas9. We demonstrate that AcrIIC2 Nme inhibits Cas9 through interactions with the positively charged bridge helix, thereby preventing sgRNA loading. In vivo phage plaque assays and in vitro DNA cleavage assays show that AcrIIC2 Nme mediates its activity through a large electronegative surface. This work shows that anti-CRISPR activity can be mediated through the inhibition of Cas9 complex assembly.

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.

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)0.000
metaresearch head score (Gemma)0.000
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 score0.189
Threshold uncertainty score0.596

Codex and Gemma teacher scores by category

CategoryCodexGemma
Metaresearch0.0000.000
Meta-epidemiology (narrow)0.0000.000
Meta-epidemiology (broad)0.0000.000
Bibliometrics0.0000.000
Science and technology studies0.0000.000
Scholarly communication0.0000.000
Open science0.0010.000
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 head0.011
GPT teacher head0.322
Teacher spread0.311 · 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