Abstract
Viruses compete with each other for limited cellular resources, and some viruses deliver defense mechanisms that protect the host from competing genetic parasites. PARIS is a defense system, often encoded in viral genomes, that is composed of a 53 kDa ABC ATPase (AriA) and a 35 kDa TOPRIM nuclease (AriB). Here we show that AriA and AriB assemble into a 425 kDa supramolecular immune complex. We use cryo-EM to determine the structure of this complex which explains how six molecules of AriA assemble into a propeller-shaped scaffold that coordinates three subunits of AriB. ATP-dependent detection of foreign proteins triggers the release of AriB, which assembles into a homodimeric nuclease that blocks infection by cleaving the host tRNALys. Phage T5 subverts PARIS immunity through expression of a tRNALys variant that prevents PARIS-mediated cleavage, and thereby restores viral infection. Collectively, these data explain how AriA functions as an ATP-dependent sensor that detects viral proteins and activates the AriB toxin. PARIS is one of an emerging set of immune systems that form macromolecular complexes for the recognition of foreign proteins, rather than foreign nucleic acids.
Competing Interest Statement
B.W. is the founder of SurGene and VIRIS Detection Systems. B.W. and A.S.F. are inventors on patent applications related to CRISPR Cas systems and applications thereof. The remaining authors declare no competing interests.
Footnotes
Labels were changed in Figure 2 Panel B to reflect the correct residues. Specifically, Residues T430 and E404 were mislabeled in the previous manuscript. Minor grammatical correction: “non-cleavage” was changed to “non-cleavable” in the legend for Figure 5