8tk0

Structure of Gabija AB complexStructure of Gabija AB complex

Structural highlights

8tk0 is a 4 chain structure with sequence from Bacillus cereus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 3.23Å
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

GAJA_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 PubMed

As one of the most prevalent anti-phage defense systems in prokaryotes, Gabija consists of a Gabija protein A (GajA) and a Gabija protein B (GajB). The assembly and function of the Gabija system remain unclear. Here we present cryo-EM structures of Bacillus cereus GajA and GajAB complex, revealing tetrameric and octameric assemblies, respectively. In the center of the complex, GajA assembles into a tetramer, which recruits two sets of GajB dimer at opposite sides of the complex, resulting in a 4:4 GajAB supramolecular complex for anti-phage defense. Further biochemical analysis showed that GajA alone is sufficient to cut double-stranded DNA and plasmid DNA, which can be inhibited by ATP. Unexpectedly, the GajAB displays enhanced activity for plasmid DNA, suggesting a role of substrate selection by GajB. Together, our study defines a framework for understanding anti-phage immune defense by the GajAB complex.

Molecular basis of Gabija anti-phage supramolecular assemblies.,Yang XY, Shen Z, Xie J, Greenwald J, Marathe I, Lin Q, Xie WJ, Wysocki VH, Fu TM Nat Struct Mol Biol. 2024 Aug;31(8):1243-1250. doi: 10.1038/s41594-024-01283-w. , Epub 2024 Apr 16. PMID:38627580^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Doron S, Melamed S, Ofir G, Leavitt A, Lopatina A, Keren M, Amitai G, Sorek R. Systematic discovery of antiphage defense systems in the microbial pangenome. Science. 2018 Mar 2;359(6379):eaar4120. PMID:29371424 doi:10.1126/science.aar4120
↑ Cheng R, Huang F, Wu H, Lu X, Yan Y, Yu B, Wang X, Zhu B. A nucleotide-sensing endonuclease from the Gabija bacterial defense system. Nucleic Acids Res. 2021 May 21;49(9):5216-5229. PMID:33885789 doi:10.1093/nar/gkab277
↑ Antine SP, Johnson AG, Mooney SE, Leavitt A, Mayer ML, Yirmiya E, Amitai G, Sorek R, Kranzusch PJ. Structural basis of Gabija anti-phage defence and viral immune evasion. Nature. 2024 Jan;625(7994):360-365. PMID:37992757 doi:10.1038/s41586-023-06855-2
↑ Cheng R, Huang F, Wu H, Lu X, Yan Y, Yu B, Wang X, Zhu B. A nucleotide-sensing endonuclease from the Gabija bacterial defense system. Nucleic Acids Res. 2021 May 21;49(9):5216-5229. PMID:33885789 doi:10.1093/nar/gkab277
↑ Yang XY, Shen Z, Xie J, Greenwald J, Marathe I, Lin Q, Xie WJ, Wysocki VH, Fu TM. Molecular basis of Gabija anti-phage supramolecular assemblies. Nat Struct Mol Biol. 2024 Aug;31(8):1243-1250. PMID:38627580 doi:10.1038/s41594-024-01283-w

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OCA

[1] Doron S, Melamed S, Ofir G, Leavitt A, Lopatina A, Keren M, Amitai G, Sorek R. Systematic discovery of antiphage defense systems in the microbial pangenome. Science. 2018 Mar 2;359(6379):eaar4120. PMID:29371424 doi:10.1126/science.aar4120

[2] Cheng R, Huang F, Wu H, Lu X, Yan Y, Yu B, Wang X, Zhu B. A nucleotide-sensing endonuclease from the Gabija bacterial defense system. Nucleic Acids Res. 2021 May 21;49(9):5216-5229. PMID:33885789 doi:10.1093/nar/gkab277

[3] Antine SP, Johnson AG, Mooney SE, Leavitt A, Mayer ML, Yirmiya E, Amitai G, Sorek R, Kranzusch PJ. Structural basis of Gabija anti-phage defence and viral immune evasion. Nature. 2024 Jan;625(7994):360-365. PMID:37992757 doi:10.1038/s41586-023-06855-2

[4] Cheng R, Huang F, Wu H, Lu X, Yan Y, Yu B, Wang X, Zhu B. A nucleotide-sensing endonuclease from the Gabija bacterial defense system. Nucleic Acids Res. 2021 May 21;49(9):5216-5229. PMID:33885789 doi:10.1093/nar/gkab277

[5] Yang XY, Shen Z, Xie J, Greenwald J, Marathe I, Lin Q, Xie WJ, Wysocki VH, Fu TM. Molecular basis of Gabija anti-phage supramolecular assemblies. Nat Struct Mol Biol. 2024 Aug;31(8):1243-1250. PMID:38627580 doi:10.1038/s41594-024-01283-w

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