Structural basis for calcium-stimulating pore formation of Vibrio α-hemolysin

Yu Chuan Chiu, Min Chi Yeh, Chun Hsiung Wang, Yu An Chen, Hsiang Chang, Han You Lin, Meng Chiao Ho, Shih Ming Lin

Research output: Contribution to journalArticlepeer-review

Abstract

Vibrio α-hemolysins (αHLs) are β-pore-forming toxins secreted by Vibrio pathogens, crucial for the facilitation of bacterial infections through host cell lysis. These toxins are produced as inactive precursors, requiring proteolytic maturation and membrane association for activation within host tissues. Here, we investigate Vibrio campbellii αHL (VcαHL), and establish that its hemolytic activity is significantly stimulated by calcium ions, with an EC50 that aligns with physiological calcium concentrations. Furthermore, we illustrate the vital contribution of calcium ions to the oligomerization of VcαHL on membranes. Using X-ray crystallography and cryo-electron microscopy, we decipher both the immature and assembled structures of VcαHL and elucidate the conformational changes corresponding to toxin assembly. We also identify a calcium-binding module that is integral for VcαHL’s calcium-dependent activation. These findings provide insights into the regulatory mechanisms of VcαHL and have the potential to inform the development of targeted therapeutic strategies against Vibrio infections.

Original languageEnglish
Article number5946
JournalNature communications
Volume14
Issue number1
DOIs
Publication statusPublished - 2023 Dec

All Science Journal Classification (ASJC) codes

  • General Chemistry
  • General Biochemistry,Genetics and Molecular Biology
  • General Physics and Astronomy

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