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Publication Abstract from PubMed

Vibrio alpha-hemolysins (alphaHLs) are beta-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 alphaHL (VcalphaHL), and establish that its hemolytic activity is significantly stimulated by calcium ions, with an EC(50) that aligns with physiological calcium concentrations. Furthermore, we illustrate the vital contribution of calcium ions to the oligomerization of VcalphaHL on membranes. Using X-ray crystallography and cryo-electron microscopy, we decipher both the immature and assembled structures of VcalphaHL and elucidate the conformational changes corresponding to toxin assembly. We also identify a calcium-binding module that is integral for VcalphaHL's calcium-dependent activation. These findings provide insights into the regulatory mechanisms of VcalphaHL and have the potential to inform the development of targeted therapeutic strategies against Vibrio infections.

Structural basis for calcium-stimulating pore formation of Vibrio alpha-hemolysin.,Chiu YC, Yeh MC, Wang CH, Chen YA, Chang H, Lin HY, Ho MC, Lin SM Nat Commun. 2023 Sep 23;14(1):5946. doi: 10.1038/s41467-023-41579-x. PMID:37741869^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.