Scholarlink

<p>Hemolysin β-pore-forming toxins (βPFTs) are key virulence factors of <i>Clostridium perfringens</i>, associated with severe diseases in humans and animals. Yet, the mechanisms by which <i>Clostridium</i> βPFTs recognize and engage specific target cells remain poorly understood. Here, we identify the cellular receptor for <i>C. perfringens</i> necrotizing enteritis toxin F (NetF), a recently discovered toxin implicated in severe enteritis in dogs and foals. We show that NetF binds to the same receptor as anthrax toxin, namely ANTXR2. Using cryo-electron microscopy, we determined the structure of the oligomeric NetF pre-pore as well as the transmembrane pore, both alone and in complex with the extracellular domain of ANTXR2. Unlike anthrax toxin, which binds to the apical MIDAS motif of ANTXR2 – as does the natural ANTXR2 ligand collagen type VI – NetF engages the receptor laterally, spanning both the von Willebrand A and the Ig-like domains. This interaction positions the toxin near the membrane, facilitating contact with membrane lipids and promoting transmembrane pore formation. Our findings uncover key principles of hemolysin βPFT-receptor recognition and advance our understanding of how pathogenic bacteria use these toxins to breach host defenses.</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

Identification and structural characterization of anthrax toxin receptor 2 as the Clostridium perfringens NetF receptor

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年2月14日

查看全文
  • Chang Wang,
  • Filippo Cattalani,
  • Ioan Iacovache,
  • Arunasalam Naguleswaran,
  • Faezeh Farhoosh,
  • Jan Franzen,
  • Laurence Abrami,
  • F. Gisou van der Goot,
  • Horst Posthaus,
  • Benoît Zuber

摘要

Hemolysin β-pore-forming toxins (βPFTs) are key virulence factors of Clostridium perfringens, associated with severe diseases in humans and animals. Yet, the mechanisms by which Clostridium βPFTs recognize and engage specific target cells remain poorly understood. Here, we identify the cellular receptor for C. perfringens necrotizing enteritis toxin F (NetF), a recently discovered toxin implicated in severe enteritis in dogs and foals. We show that NetF binds to the same receptor as anthrax toxin, namely ANTXR2. Using cryo-electron microscopy, we determined the structure of the oligomeric NetF pre-pore as well as the transmembrane pore, both alone and in complex with the extracellular domain of ANTXR2. Unlike anthrax toxin, which binds to the apical MIDAS motif of ANTXR2 – as does the natural ANTXR2 ligand collagen type VI – NetF engages the receptor laterally, spanning both the von Willebrand A and the Ig-like domains. This interaction positions the toxin near the membrane, facilitating contact with membrane lipids and promoting transmembrane pore formation. Our findings uncover key principles of hemolysin βPFT-receptor recognition and advance our understanding of how pathogenic bacteria use these toxins to breach host defenses.