Structural basis for Lamassu-based antiviral immunity and its evolution from DNA repair machinery DOI Creative Commons
Matthieu Haudiquet, A. Chakravarti, Zhiying Zhang

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Апрель 2, 2025

Bacterial immune systems exhibit remarkable diversity and modularity, as a consequence of the continuous selective pressures imposed by phage predation. Despite recent mechanistic advances, evolutionary origins many antiphage remain elusive, especially for those that encode homologs Structural Maintenance Chromosomes (SMC) superfamily, which are essential chromosome maintenance DNA repair across domains life. Here, we elucidate structural basis emergence Lamassu, bacterial system family featuring diverse effectors but core conserved SMC-like sensor. Using cryo-EM, determined structures Vibrio cholerae Lamassu complex in both apo- dsDNA-bound states, revealing unexpected stoichiometry topological architectures. We further demonstrate how specifically senses dsDNA vitro replication vivo , thereby triggering formation LmuA tetramers activate Cap4 nuclease domain. Our findings reveal evolved via exaptation Rad50-Mre11 to form compact, modular sensor viral replication, exemplifying cellular machinery can be co-opted novel functions.

Язык: Английский

Structural basis for Lamassu-based antiviral immunity and its evolution from DNA repair machinery DOI Creative Commons
Matthieu Haudiquet, A. Chakravarti, Zhiying Zhang

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown

Опубликована: Апрель 2, 2025

Bacterial immune systems exhibit remarkable diversity and modularity, as a consequence of the continuous selective pressures imposed by phage predation. Despite recent mechanistic advances, evolutionary origins many antiphage remain elusive, especially for those that encode homologs Structural Maintenance Chromosomes (SMC) superfamily, which are essential chromosome maintenance DNA repair across domains life. Here, we elucidate structural basis emergence Lamassu, bacterial system family featuring diverse effectors but core conserved SMC-like sensor. Using cryo-EM, determined structures Vibrio cholerae Lamassu complex in both apo- dsDNA-bound states, revealing unexpected stoichiometry topological architectures. We further demonstrate how specifically senses dsDNA vitro replication vivo , thereby triggering formation LmuA tetramers activate Cap4 nuclease domain. Our findings reveal evolved via exaptation Rad50-Mre11 to form compact, modular sensor viral replication, exemplifying cellular machinery can be co-opted novel functions.

Язык: Английский

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