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TitleStructural basis for calcium-stimulating pore formation of Vibrio α-hemolysin.
Journal, issue, pagesNat Commun, Vol. 14, Issue 1, Page 5946, Year 2023
Publish dateSep 23, 2023
AuthorsYu-Chuan Chiu / Min-Chi Yeh / Chun-Hsiung Wang / Yu-An Chen / Hsiang Chang / Han-You Lin / Meng-Chiao Ho / Shih-Ming Lin /
PubMed AbstractVibrio 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 ...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.
External linksNat Commun / PubMed:37741869 / PubMed Central
MethodsEM (single particle) / X-ray diffraction
Resolution2 - 2.06 Å
Structure data

EMDB-36150, PDB-8jc7:
Cryo-EM structure of Vibrio campbellii alpha-hemolysin
Method: EM (single particle) / Resolution: 2.06 Å

PDB-8jbq:
Pro-alpha-hemolysin of Vibrio campbellii
Method: X-RAY DIFFRACTION / Resolution: 2.0 Å

Chemicals

ChemComp-SO4:
SULFATE ION / Sulfate

ChemComp-HOH:
WATER / Water

ChemComp-K:
Unknown entry

ChemComp-CA:
Unknown entry

Source
  • vibrio campbellii (bacteria)
KeywordsTOXIN / Hemolysin / Pore forming toxin / Vibrio campbellii alpha-hemolysin / Pore-forming toxins (PFTs) / Calcium-dependent oligomerization / Membrane association / Structure-function relationship

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