Evidence map›Paper›PMID 40277083›Full record

ArticleNucleic acids research2025

Mechanism of Cas9 inhibition by AcrIIA11.

Kaylee E Dillard, Hongshan Zhang, Lianne Z Dubbs, Chia-Wei Chou, Cynthia Terrace, Kamyab Javanmardi, Wantae Kim, Kevin J Forsberg, Ilya J Finkelstein

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nucleic acids research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
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

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Review
  4. Article
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

9 authors.

Kaylee E DillardDepartment of Molecular Biosciences and Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, United States.
Hongshan ZhangDepartment of Molecular Biosciences and Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, United States.
Lianne Z DubbsDepartment of Molecular Biosciences and Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, United States.
Chia-Wei ChouDepartment of Molecular Biosciences and Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, United States.
Cynthia TerraceDepartment of Molecular Biosciences and Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, United States.
Kamyab JavanmardiDepartment of Molecular Biosciences and Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, United States.
Wantae KimDepartment of Molecular Biosciences and Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, United States.
Kevin J ForsbergDepartment of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX 75390, United States.
Ilya J FinkelsteinDepartment of Molecular Biosciences and Institute for Cellular and Molecular Biology, University of Texas at Austin, Austin, TX 78712, United States.ORCID 0000-0002-9371-2431

Funding

Discovery of bacterial defense and phage counter-defense strategiesDP2AI154402 · NIAID · UT SOUTHWESTERN MEDICAL CENTER · PI FORSBERG, KEVIN J · 2021 to 2025
$2.6M
Gene-specific transcriptional silencing directed by dephosphorylation of RNAP IIR01GM104896 · NIGMS · UNIVERSITY OF TEXAS AT AUSTIN · PI ZHANG, YAN JESSIE · 2013 to 2022
$2.4M
Mechanism, specificity, and design of CRISPR RNA-mediated gene regulationR01GM124141 · NIGMS · UNIVERSITY OF TEXAS AT AUSTIN · PI FINKELSTEIN, ILYA J · 2017 to 2020
$1.2M
Dynamic target recognition and complex assembly of the Type I-E CRISPR-Cas systemF31GM125201 · NIGMS · UNIVERSITY OF TEXAS AT AUSTIN · PI DILLARD, KAYLEE E · 2018 to 2020
$81k
Howard Hughes Medical Institute Emerging Pathogens InitiativeNIAID NIH HHS DP2 AI154402NIGMS NIH HHS F31 GM125201NIGMS NIH HHS R01 GM104896NIGMS NIH HHS R01 GM124141NIH HHS R01GM124141Searle Scholars AwardUniversity of Texas Southwestern Medical CenterWelch Foundation F-1808
6 · The paper itself

Abstract

Mobile genetic elements evade CRISPR-Cas adaptive immunity by encoding anti-CRISPR proteins (Acrs). Acrs inactivate CRISPR-Cas systems via diverse mechanisms but generally coevolve with a narrow subset of Cas effectors that share high sequence similarity. Here, we demonstrate that AcrIIA11 inhibits Streptococcus pyogenes (Sp), Staphylococcus aureus (Sa), and Francisella novicida (Fn) Cas9s in vitro and in human cells. Single-molecule imaging reveals that AcrIIA11 hinders SaCas9 target search by reducing its diffusion on nonspecific DNA. DNA cleavage is inhibited because the AcrIIA11:SaCas9 complex binds to protospacer adjacent motif (PAM)-rich off-target sites, preventing SaCas9 from reaching its target. AcrIIA11 also greatly slows down DNA cleavage after SaCas9 reaches its target site. A negative-stain electron microscopy reconstruction of an AcrIIA11:SaCas9 RNP complex reveals that the heterodimer assembles with a 1:1 stoichiometry. Physical AcrIIA11-Cas9 interactions across type IIA and IIB Cas9s correlate with nuclease inhibition and support its broad-spectrum activity. These results add a kinetic inhibition mechanism to the phage-CRISPR arms race.

Indexed as

Bacterial ProteinsCRISPR-Associated Protein 9CRISPR-Cas SystemsDNADNA CleavageFrancisellaHEK293 CellsHumansStaphylococcus aureusStreptococcus pyogenesBacterial ProteinsCRISPR-Associated Protein 9DNA

Identifiers

PMID40277083
PMCPMC12022753

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

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 Socratic graph.