8JC7

Cryo-EM structure of Vibrio campbellii alpha-hemolysin

Summary for 8JC7

• Entry DOI: 10.2210/pdb8jc7/pdb
• Related: 8JBQ
• EMDB information: 36150
• Descriptor: Hemolysin, POTASSIUM ION, CALCIUM ION, ... (4 entities in total)
• Functional Keywords: vibrio campbellii alpha-hemolysin, pore-forming toxins (pfts), calcium-dependent oligomerization, membrane association, structure-function relationship, toxin
• Biological source: Vibrio campbellii
• Total number of polymer chains: 7
• Total formula weight: 565059.28

Authors

Wang, C.H.,Yeh, M.K.,Ho, M.C.,Lin, S.M. (deposition date: 2023-05-10, release date: 2023-09-27, Last modification date: 2024-11-13)

Primary citation

Chiu, Y.C.,Yeh, M.C.,Wang, C.H.,Chen, Y.A.,Chang, H.,Lin, H.Y.,Ho, M.C.,Lin, S.M.
Structural basis for calcium-stimulating pore formation of Vibrio alpha-hemolysin.
Nat Commun, 14:5946-5946, 2023

PubMed 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 EC 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.

PubMed: 37741869
DOI: 10.1038/s41467-023-41579-x

Experimental method

ELECTRON MICROSCOPY (2.06 Å)