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Updated: Feb 14, 2026

Sequence-specific Labeling of Nucleic Acids and Proteins with Methyltransferases and Cofactor Analogues
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Published on: November 22, 2014

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Bacterial Cofactors for CRISPR Activation

Zhipeng Wang1, Yujue Wang1, Quanjiang Ji1,2,3

  • 1School of Physical Science and Technology & State Key Laboratory of Advanced Medical Materials and Devices, ShanghaiTech University, Shanghai 201210, China.

Biochemistry
|February 12, 2026
PubMed

Insights

Bacterial thioredoxin (TrxA) enhances the DNA cleavage activity of the Cas12p enzyme. This interaction, mediated by a redox-sensitive binding domain, reveals that CRISPR-Cas systems are modulated by auxiliary factors.

Area of Science:

  • Molecular Biology
  • Microbiology
  • Biochemistry

Background:

  • CRISPR-Cas systems provide adaptive immunity in prokaryotes against foreign genetic elements.
  • While anti-CRISPR proteins are well-studied, host factors that enhance Cas effector activity are less understood.
  • Cas12p, a compact type V nuclease, is a phage-associated enzyme with implications in CRISPR-Cas immunity.

Purpose of the Study:

  • To investigate host factors that modulate the activity of the Cas12p nuclease.
  • To elucidate the mechanism by which bacterial thioredoxin (TrxA) influences Cas12p function.

Main Methods:

  • Biochemical assays to measure Cas12p DNA cleavage activity.
  • Protein-protein interaction studies to analyze TrxA binding to Cas12p.
  • Structural analysis of the Cas12p-TrxA complex.

Main Results:

  • Bacterial thioredoxin (TrxA) was identified as a crucial factor for efficient DNA cleavage by Cas12p.
  • TrxA binds to a specific thioredoxin-binding (TB) domain on Cas12p.
  • The interaction between TrxA and Cas12p is redox-sensitive and promotes an active conformation for DNA cleavage.

Conclusions:

  • Host proteins, like TrxA, can act as activators of CRISPR-Cas effectors, such as Cas12p.
  • CRISPR-Cas immunity is a dynamic network influenced by auxiliary factors that fine-tune effector activity.
  • This discovery expands the known repertoire of CRISPR-Cas modulators and highlights the complexity of microbial defense systems.

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