Abstact

Bacteria have developed a variety of immune systems to combat phage infections. The Lamassu system is a prokaryotic immune system with a core conserved structural maintenance of chromosomes (SMC) superfamily protein LmuB and diverse effectors named LmuA, whose mechanism remains unclear. Here we present a series of cryo-electron microscopy structures of the type-I Lamassu complex from Bacillus cellulasensis and the type-II Lamassu complex from Vibrio cholerae, both in apo and dsDNA-bound states, revealing an unexpected stoichiometry and topological architecture distinct from canonical SMC complexes. Combined structural and biochemical analyses show how the nuclease effector LmuA is sequestered in an inactive monomeric form within the Lamassu complex and, upon sensing foreign DNA ends, dissociates and assembles into an active tetramer capable of DNA cleavage. Our findings elucidate the mechanism by which Lamassu systems detect viral replication and implement antiphage defense, highlighting the roles of SMC proteins in prokaryotic immunity.