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


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.

SUBMITTER: Chiu YC 

PROVIDER: S-EPMC10517994 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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

Chiu Yu-Chuan YC   Yeh Min-Chi MC   Wang Chun-Hsiung CH   Chen Yu-An YA   Chang Hsiang H   Lin Han-You HY   Ho Meng-Chiao MC   Lin Shih-Ming SM  

Nature communications 20230923 1


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 EC<sub>50</sub> that aligns with physiological c  ...[more]

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