Download MendeleyDirect activation of a bacterial innate immune system by a viral capsid protein.
Zhang, T., Tamman, H., Coppieters 't Wallant, K., Kurata, T., LeRoux, M., Srikant, S., Brodiazhenko, T., Cepauskas, A., Talavera, A., Martens, C., Atkinson, G.C., Hauryliuk, V., Garcia-Pino, A., Laub, M.T.(2022) Nature 612: 132-140
- PubMed: 36385533
- DOI: https://doi.org/10.1038/s41586-022-05444-z
- Primary Citation of Related Structures:
7ZTB - PubMed Abstract:
Bacteria have evolved diverse immunity mechanisms to protect themselves against the constant onslaught of bacteriophages 1-3 . Similar to how eukaryotic innate immune systems sense foreign invaders through pathogen-associated molecular patterns 4 (PAMPs), many bacterial immune systems that respond to bacteriophage infection require phage-specific triggers to be activated. However, the identities of such triggers and the sensing mechanisms remain largely unknown. Here we identify and investigate the anti-phage function of CapRel SJ46 , a fused toxin-antitoxin system that protects Escherichia coli against diverse phages. Using genetic, biochemical and structural analyses, we demonstrate that the C-terminal domain of CapRel SJ46 regulates the toxic N-terminal region, serving as both antitoxin and phage infection sensor. Following infection by certain phages, newly synthesized major capsid protein binds directly to the C-terminal domain of CapRel SJ46 to relieve autoinhibition, enabling the toxin domain to pyrophosphorylate tRNAs, which blocks translation to restrict viral infection. Collectively, our results reveal the molecular mechanism by which a bacterial immune system directly senses a conserved, essential component of phages, suggesting a PAMP-like sensing model for toxin-antitoxin-mediated innate immunity in bacteria. We provide evidence that CapRels and their phage-encoded triggers are engaged in a 'Red Queen conflict' 5 , revealing a new front in the intense coevolutionary battle between phages and bacteria. Given that capsid proteins of some eukaryotic viruses are known to stimulate innate immune signalling in mammalian hosts 6-10 , our results reveal a deeply conserved facet of immunity.
Organizational Affiliation:
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA.
