Structural basis of Gabija anti-phage defence and viral immune evasion

Antine, Sadie P.; Johnson, Alex G.; Mooney, Sarah E.; Leavitt, Azita; Mayer, Megan L.; Yirmiya, Erez; Amitai, Gil; Sorek, Rotem; Kranzusch, Philip J.

doi:10.1038/s41586-023-06855-2

Structural basis of Gabija anti-phage defence and viral immune evasion

Journal Article · Wed Nov 22 00:00:00 EST 2023 · Nature (London)

DOI:https://doi.org/10.1038/s41586-023-06855-2· OSTI ID:2470219

^[1]; ^[1]; Mooney, Sarah E. ^[1]; Leavitt, Azita ^[2]; Mayer, Megan L. ^[3]; Yirmiya, Erez ^[2]; ^[2]; ^[2]; ^[1]

Harvard Medical School, Boston, MA (United States); Dana-Farber Cancer Institute, Boston, MA (United States)
Weizmann Institute of Science, Rehovot (Israel)
Harvard Medical School, Boston, MA (United States)

Bacteria encode hundreds of diverse defence systems that protect them from viral infection and inhibit phage propagation. Gabija is one of the most prevalent anti-phage defence systems, occurring in more than 15% of all sequenced bacterial and archaeal genomes, but the molecular basis of how Gabija defends cells from viral infection remains poorly understood. Here we use X-ray crystallography and cryo-electron microscopy (cryo-EM) to define how Gabija proteins assemble into a supramolecular complex of around 500 kDa that degrades phage DNA. Gabija protein A (GajA) is a DNA endonuclease that tetramerizes to form the core of the anti-phage defence complex. Two sets of Gabija protein B (GajB) dimers dock at opposite sides of the complex and create a 4:4 GajA–GajB assembly (hereafter, GajAB) that is essential for phage resistance in vivo. We show that a phage-encoded protein, Gabija anti-defence 1 (Gad1), directly binds to the Gabija GajAB complex and inactivates defence. A cryo-EM structure of the virally inhibited state shows that Gad1 forms an octameric web that encases the GajAB complex and inhibits DNA recognition and cleavage. Our results reveal the structural basis of assembly of the Gabija anti-phage defence complex and define a unique mechanism of viral immune evasion.

View Accepted Manuscript (DOE)

Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: Deutsche Forschungsgemeinschaft; European Research Council (ERC); Israel Science Foundation; National Institutes of Health (NIH); USDOE Office of Science (SC), Basic Energy Sciences (BES). Scientific User Facilities (SUF); USDOE Office of Science (SC), Biological and Environmental Research (BER)

Grant/Contract Number:: AC02-06CH11357

OSTI ID:: 2470219

Journal Information:: Nature (London), Journal Name: Nature (London) Journal Issue: 7994 Vol. 625; ISSN 0028-0836

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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