Summary information and primary citation
- PDB-id
-
8x51;
DSSR-derived features in text and
JSON formats; DNAproDB
- Class
- DNA binding protein-DNA
- Method
- cryo-EM (2.92 Å)
- Summary
- Structure of DNA-bound gaja dimer (focused
refinement)
- Reference
-
Li J, Cheng R, Wang Z, Yuan W, Xiao J, Zhao X, Du X, Xia
S, Wang L, Zhu B, Wang L (2024): "Structures
and activation mechanism of the Gabija anti-phage
system." Nature, 629,
467-473. doi: 10.1038/s41586-024-07270-x.
- Abstract
- Prokaryotes have evolved intricate innate immune
systems against phage infection<sub>1-7</sub>.
Gabija is a highly abundant prokaryotic defense system
consisting of two components, GajA and
GajB<sub>8</sub>. We previously demonstrated
that GajA functions as a DNA endonuclease that is inactive
in the presence of ATP<sub>9</sub>. To reveal
how the Gabija system is activated for anti-phage defense,
we report its cryo-electron microscopy (cryo-EM) 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/Mg<sub>2+</sub>. GajA is a
rhombus-shaped tetramer with its ATPase domain clustered at
the center and the 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 Gajiba activation.
