The anti-phage mechanism of a widespread trypsin-MBL module
Huang, P.; Liu, J.; Guo, L. G.; Xu, D.; Shen, L. S.; Pu rui, Y.; Tong, C.; Fei, W.; Cheng, M.; Li, Z.; Lu, M.; Zhang, L.; Wu, N.; Qi, L.; Xiao, Y.; Chen, M.
Show abstract
Protease mediate activation of immune effectors is a conserved mechanism across life. This study identified a widespread and co-evolving trypsin-MBL module as a core effector in diverse bacterial immune systems (e.g., Hachiman, Argonaute, AVAST), protecting host via abortive infection. Focusing on Hachiman-trypsin-MBL, we demonstrated that, the protease activity of trypsin*HamAB is inhibited in the presence of ATP and MBL is an autoinhibited DNase with two inserted loops blocking the catalytic pocket. Upon infection, the HamB helicase senses invading nucleic acids and catalyzes the hydrolysis of ATP, activating the associated trypsin-like protease that cleaves specifically at two non-canonical KSS motif of MBL and releases its DNase activity. Cryo-EM structures of activated trypsin*HamAB bound with DNA reveal DNA binding and ATP hydrolysis lead to the release of the trypsin-like domain, enabling activation. Our work provides a comprehensive understanding on the mechanism of widely distributed trypsin-MBL module, wherein proteolytic activation of a toxic nuclease enables robust bacterial immunity while preventing self-toxicity through multi-layered control.
Matching journals
The top 6 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
- Long-read sequencing reveals extensive DNA methylations in human gut phagenome contributed by prevalently phage-encoded methyltransferases 93%
- IgG-Bridging-Seeded Synergistic Aggregation of SARS-CoV-2 Spikes Underlies Potent Neutralization by A Low-Affinity Antibody 92%
- UCHL3 regulates subgenomic flaviviral RNA condensates to promote virus propagation 91%
Similar papers in this journal
- Substrate selectivity and catalytic activation of the type III CRISPR ancillary nuclease Can2 95%
- Expanding the Landscape of BREX Diversity: Uncovering Multi-Layered Functional Frameworks and Identification of Novel BREX-Related Defense Systems 95%
- Exploring the diversity of anti-defense systems across prokaryotes, phages, and mobile genetic elements 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.