The Gabija gene occurs in more than 15% of sequenced bacterial and archaeal genomes, making it one of the most abundant defense systems against phages in prokaryotes. However, the assembly form of the Gabija system molecular machine and the structural basis for its protection of prokaryotes against phage infection have remained unclear.

A research group led by Prof. WEI Taotao from the Institute of Biophysics of the Chinese Academy of Sciences, together with Prof. MA Jun from the Shenzhen Bay Laboratory, has revealed the structure of the Gabija complex and elucidated the molecular mechanism by which the Gabija system functions in immune defense.

This study was published in Nature Communications.

The researchers found that the Gabija complex is an octamer consisting of four GajA proteins and four GajB proteins. The Gabija complex has sequence-specific DNA endonuclease activity and prefers circular DNA as a substrate.

Based on cryo-electron microscopy structural analysis and biochemical experiments, the researchers proposed a model for the antiviral mechanism of the Gabija immune system: under normal physiological conditions, the high concentration of nucleoside triphosphates (NTPs) and deoxynucleotide triphosphates (dNTPs) in the cell inhibits the endonuclease activity of the Gabija complex. However, during phage invasion, high-intensity replication, and transcription of viral DNA, depletion of NTPs and dNTPs rapidly activates the Gabija complex. This complex first cleaves circular DNA to inhibit phage DNA replication, thereby blocking phage amplification.

This study reveals the molecular mechanism by which the Gabija system senses phage invasion and its preference for cleaving DNA substrates. It also provides new avenues for research into host anti-phage immunity. Additionally, the Gabija system holds promise to provide important structural and biochemical foundations for the development of molecular biology tools.

The Gabija complex octameric ring structure (Image by WEI Taotao's group)  

Molecular mechanism of Gabija system against phage infection (Image by WEI Taotao's group)