Scholarlink

<p>Lamassu is a diverse family of defense systems that protect bacteria, including seventh-pandemic strains of <i>Vibrio</i> <i>cholerae</i>, against both plasmids and phage infection. During phage infection, Lamassu targets essential cellular processes, thereby halting phage propagation by terminating the infected host. The mechanisms by which Lamassu effectors are activated when needed and otherwise suppressed are unknown. Here we present structures of a Lamassu defense system from <i>Salmonella</i> <i>enterica</i>. We show that an oligomerization domain of the nuclease effector subunit, LmuA, is sequestered by two tightly folded SMC-like LmuB protomers and LmuC. Upon activation, liberated LmuA assembles into homotetramers, in which two of four nuclease domains are brought into proximity to create an active site capable of cleaving DNA. We propose that tetramer formation is likely a one-way switch that establishes a threshold to limit potential spontaneous activation and cell death. Our findings reveal a mechanism of cellular defense, involving liberation and oligomerization of immune effectors, and shed light on how Lamassu systems balance potent immune responses with self-preservation.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Structure and activation mechanism of a Lamassu phage and plasmid defense system

  • 期刊论文

  • 发表日期：

    2025年10月14日

查看全文
  • Yan Li,
  • David W. Adams,
  • Hon Wing Liu,
  • Steven J. Shaw,
  • Emiko Uchikawa,
  • Milena Jaskólska,
  • Sandrine Stutzmann,
  • Laurie Righi,
  • Mark D. Szczelkun,
  • Melanie Blokesch,
  • Stephan Gruber

摘要

Lamassu is a diverse family of defense systems that protect bacteria, including seventh-pandemic strains of Vibrio cholerae, against both plasmids and phage infection. During phage infection, Lamassu targets essential cellular processes, thereby halting phage propagation by terminating the infected host. The mechanisms by which Lamassu effectors are activated when needed and otherwise suppressed are unknown. Here we present structures of a Lamassu defense system from Salmonella enterica. We show that an oligomerization domain of the nuclease effector subunit, LmuA, is sequestered by two tightly folded SMC-like LmuB protomers and LmuC. Upon activation, liberated LmuA assembles into homotetramers, in which two of four nuclease domains are brought into proximity to create an active site capable of cleaving DNA. We propose that tetramer formation is likely a one-way switch that establishes a threshold to limit potential spontaneous activation and cell death. Our findings reveal a mechanism of cellular defense, involving liberation and oligomerization of immune effectors, and shed light on how Lamassu systems balance potent immune responses with self-preservation.