Structural insights into type-I and type-II Lamassu antiphage systems.

Area of Science:

• Microbiology
• Structural Biology
• Immunology

Background:

• Bacteria possess diverse defense mechanisms against bacteriophage infections.
• The Lamassu system is a prokaryotic immune system utilizing SMC superfamily proteins (LmuB) and effectors (LmuA).
• The precise mechanism of Lamassu-mediated antiphage defense remains largely uncharacterized.

Purpose of the Study:

• To elucidate the structural basis and mechanism of the Lamassu antiphage defense system.
• To investigate the role of SMC proteins in bacterial immunity.
• To understand how the LmuA effector is regulated within the Lamassu complex.

Main Methods:

• Cryo-electron microscopy (cryo-EM) to determine the structures of Type-I and Type-II Lamassu complexes.
• Biochemical analyses to assess protein function and interactions.
• Structural and biochemical data integration to reveal functional mechanisms.

Main Results:

• Determined cryo-EM structures of Lamassu complexes from *Bacillus cellulasensis* and *Vibrio cholerae* in apo and dsDNA-bound states.
• Revealed an unexpected stoichiometry and topological architecture distinct from canonical SMC complexes.
• Demonstrated that the LmuA nuclease is sequestered in an inactive monomeric form and becomes active upon sensing foreign DNA ends, forming a tetramer.

Conclusions:

• Elucidated the mechanism of Lamassu-mediated antiphage defense, involving sensing viral DNA and activating nuclease effectors.
• Highlighted the crucial role of SMC proteins in bacterial adaptive immunity.
• Provided insights into the regulation and activation of the LmuA effector during phage infection.