Bacterial Hachiman complex executes DNA cleavage for antiphage defense

Area of Science:

• Molecular Biology
• Structural Biology
• Microbiology

Background:

• Bacteria possess diverse immune systems to defend against bacteriophage infections.
• The Hachiman system, composed of HamA and HamB proteins, is a recently identified prokaryotic antiphage defense mechanism.
• The precise mechanism of Hachiman system's defense activity is not fully elucidated.

Purpose of the Study:

• To determine the structural basis of the Hachiman antiphage defense system.
• To elucidate the functional roles of HamA and HamB proteins in bacterial immunity.
• To understand the interaction between nuclease and helicase domains in phage defense.

Main Methods:

• Cryo-electron microscopy (cryo-EM) was employed to resolve the structure of the Hachiman complex.
• Bioinformatics analysis was performed to investigate domain functions and evolutionary relationships.
• Biochemical assays were utilized to study protein interactions and enzymatic activities.

Main Results:

• The cryo-EM structure revealed a Hachiman complex with a fused Cap4 nuclease domain in HamA.
• The DUF1837 domain in HamA, structurally similar to PD-(D/E)XK nucleases, lacks catalytic activity.
• HamA and HamB form a heterodimer (HamAB) that mediates ATP hydrolysis and DNA cleavage for antiphage defense.

Conclusions:

• The study elucidates the structural architecture of the Hachiman defense complex.
• The findings highlight the synergistic roles of helicase and nuclease activities in prokaryotic immunity.
• This work provides insights into the molecular mechanisms underlying bacterial defense against phages.