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Structure of the phage immune evasion protein Gad1 bound to the Gabija GajAB complex
Structural highlights
FunctionGAJA_BACC6 Component of antiviral defense system Gabija type I, composed of GajA and GajB (PubMed:29371424). Endonuclease that nicks double-stranded DNA within the sequence 5'-TNNNCGGGNNA-3' in the absence of nucleotides (NTP, dNTP and NDPs), cleaving after C-1 (PubMed:33885789, PubMed:37992757). Has no detected ATPase activity (PubMed:33885789). Expression of Gabija type I in B.subtilis (strain BEST7003) confers resistance to phages phi105, phi29, rho14, SpBeta and SBSphiC (PubMed:29371424). Expression of Gabija type I in E.coli B (strain ATCC 11303) confers resistance to phage T7 (PubMed:33885789). It is thought that this enzyme is strongly suppressed during physiological growth (in E.coli total nucleotide concentration is over 8.7 mM in mid-log phase), but during viral replication, when nucleotides are rapidly consumed, it is de-suppressed and degrades target DNA (Probable).[1] [2] [3] [4] Publication Abstract from PubMedBacteria encode hundreds of diverse defence systems that protect them from viral infection and inhibit phage propagation(1-5). Gabija is one of the most prevalent anti-phage defence systems, occurring in more than 15% of all sequenced bacterial and archaeal genomes(1,6,7), 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. Structural basis of Gabija anti-phage defence and viral immune evasion.,Antine SP, Johnson AG, Mooney SE, Leavitt A, Mayer ML, Yirmiya E, Amitai G, Sorek R, Kranzusch PJ Nature. 2024 Jan;625(7994):360-365. doi: 10.1038/s41586-023-06855-2. Epub 2023 , Nov 22. PMID:37992757[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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