A virally-encoded tRNA neutralizes the PARIS antiviral defence system
(2024) In Nature- Abstract
Viruses compete with each other for limited cellular resources, and some deliver defense mechanisms that protect the host from competing genetic parasites 1. PARIS is a defense system, often encoded in viral genomes, that is composed of a 55 kDa ABC ATPase (AriA) and a 35 kDa TOPRIM nuclease (AriB) 2. However, the mechanism by which AriA and AriB function in phage defense is unknown. 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... (More)
Viruses compete with each other for limited cellular resources, and some deliver defense mechanisms that protect the host from competing genetic parasites 1. PARIS is a defense system, often encoded in viral genomes, that is composed of a 55 kDa ABC ATPase (AriA) and a 35 kDa TOPRIM nuclease (AriB) 2. However, the mechanism by which AriA and AriB function in phage defense is unknown. 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 host tRNA Lys. Phage T5 subverts PARIS immunity through expression of a tRNA Lys variant that is not cleaved by PARIS, 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 3.
(Less)
- author
- organization
- publishing date
- 2024-08-07
- type
- Contribution to journal
- publication status
- epub
- subject
- in
- Nature
- publisher
- Nature Publishing Group
- external identifiers
-
- pmid:39111359
- ISSN
- 0028-0836
- DOI
- 10.1038/s41586-024-07874-3
- language
- English
- LU publication?
- yes
- additional info
- © 2024. The Author(s), under exclusive licence to Springer Nature Limited.
- id
- d64fa582-2c25-4f95-82f9-077ebd54c884
- date added to LUP
- 2024-08-16 16:10:40
- date last changed
- 2024-08-19 07:50:29
@article{d64fa582-2c25-4f95-82f9-077ebd54c884, abstract = {{<p>Viruses compete with each other for limited cellular resources, and some deliver defense mechanisms that protect the host from competing genetic parasites 1. PARIS is a defense system, often encoded in viral genomes, that is composed of a 55 kDa ABC ATPase (AriA) and a 35 kDa TOPRIM nuclease (AriB) 2. However, the mechanism by which AriA and AriB function in phage defense is unknown. 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 host tRNA Lys. Phage T5 subverts PARIS immunity through expression of a tRNA Lys variant that is not cleaved by PARIS, 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 3. </p>}}, author = {{Burman, Nathaniel and Belukhina, Svetlana and Depardieu, Florence and Wilkinson, Royce A and Skutel, Mikhail and Santiago-Frangos, Andrew and Graham, Ava B and Livenskyi, Alexei and Chechenina, Anna and Morozova, Natalia and Zahl, Trevor and Henriques, William S and Buyukyoruk, Murat and Rouillon, Christophe and Saudemont, Baptiste and Shyrokova, Lena and Kurata, Tatsuaki and Hauryliuk, Vasili and Severinov, Konstantin and Groseille, Justine and Thierry, Agnès and Koszul, Romain and Tesson, Florian and Bernheim, Aude and Bikard, David and Wiedenheft, Blake and Isaev, Artem}}, issn = {{0028-0836}}, language = {{eng}}, month = {{08}}, publisher = {{Nature Publishing Group}}, series = {{Nature}}, title = {{A virally-encoded tRNA neutralizes the PARIS antiviral defence system}}, url = {{http://dx.doi.org/10.1038/s41586-024-07874-3}}, doi = {{10.1038/s41586-024-07874-3}}, year = {{2024}}, }