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TitleStructures and activation mechanism of the Gabija anti-phage system.
Journal, issue, pagesNature, Year 2024
Publish dateMar 12, 2024
AuthorsJing Li / Rui Cheng / Zhiming Wang / Wuliu Yuan / Jun Xiao / Xinyuan Zhao / Xinran Du / Shiyu Xia / Lianrong Wang / Bin Zhu / Longfei Wang /
PubMed AbstractProkaryotes have evolved intricate innate immune systems against phage infection. Gabija is a highly widespread prokaryotic defence system that consists of two components, GajA and GajB. GajA ...Prokaryotes have evolved intricate innate immune systems against phage infection. Gabija is a highly widespread prokaryotic defence system that consists of two components, GajA and GajB. GajA functions as a DNA endonuclease that is inactive in the presence of ATP. 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. 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.
External linksNature / PubMed:38471529
MethodsEM (single particle)
Resolution2.66 - 3.39 Å
Structure data

36541

8jq9

EMDB-36541, PDB-8jq9:
Novel Anti-phage System
Method: EM (single particle) / Resolution: 2.66 Å

36563

8jqb

EMDB-36563, PDB-8jqb:
Structure of Gabija GajA-GajB 4:4 Complex
Method: EM (single particle) / Resolution: 3.2 Å

36569

8jqc

EMDB-36569, PDB-8jqc:
Novel Anti-phage System
Method: EM (single particle) / Resolution: 3.39 Å

37915

8wy4

EMDB-37915, PDB-8wy4:
GajA tetramer with ATP
Method: EM (single particle) / Resolution: 2.81 Å

37916

8wy5

EMDB-37916, PDB-8wy5:
Structure of Gabija GajA in complex with DNA
Method: EM (single particle) / Resolution: 3.12 Å

38058

8x51

EMDB-38058, PDB-8x51:
Cryo-EM structure of Gabija GajA in complex with DNA(focused refinement)
Method: EM (single particle) / Resolution: 2.92 Å

38070

8x5i

EMDB-38070, PDB-8x5i:
tetramer Gabija with ATP (local refinement)
Method: EM (single particle) / Resolution: 3.01 Å

38071

8x5n

EMDB-38071, PDB-8x5n:
Tetramer Gabija with ATP
Method: EM (single particle) / Resolution: 2.8 Å

Chemicals

ChemComp-ATP:
ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying molecule*YM / Adenosine triphosphate

ChemComp-CA:
Unknown entry

ChemComp-MG:
Unknown entry

Source
  • bacillus cereus (strain vd045) (bacteria)
  • bacillus cereus vd045 (bacteria)
  • synthetic construct (others)
KeywordsIMMUNE SYSTEM / Anti-Phage / DNA BINDING PROTEIN / endonuclease / Complex / DNA BINDING / DNA BINDING PROTEIN/DNA / DNA BINDING PROTEIN-DNA complex / Anti-Phage System

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