8wy4
GajA tetramer with ATP
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 PubMedProkaryotes have evolved intricate innate immune systems against phage infection(1-7). Gabija is a highly widespread prokaryotic defence system that consists of two components, GajA and GajB(8). GajA functions as a DNA endonuclease that is inactive in the presence of ATP(9). Here, to explore how the Gabija system is activated for anti-phage defence, we report its cryo-electron microscopy structures in five states, including apo GajA, GajA in complex with DNA, GajA bound by ATP, apo GajA-GajB, and GajA-GajB in complex with ATP and Mg(2+). GajA is a rhombus-shaped tetramer with its ATPase domain clustered at the centre and the topoisomerase-primase (Toprim) domain located peripherally. ATP binding at the ATPase domain stabilizes the insertion region within the ATPase domain, keeping the Toprim domain in a closed state. Upon ATP depletion by phages, the Toprim domain opens to bind and cleave the DNA substrate. GajB, which docks on GajA, is activated by the cleaved DNA, ultimately leading to prokaryotic cell death. Our study presents a mechanistic landscape of Gabija activation. Structures and activation mechanism of the Gabija anti-phage system.,Li J, Cheng R, Wang Z, Yuan W, Xiao J, Zhao X, Du X, Xia S, Wang L, Zhu B, Wang L Nature. 2024 May;629(8011):467-473. doi: 10.1038/s41586-024-07270-x. Epub 2024 , Mar 12. PMID:38471529[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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