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bioRxiv · 10.1101/2022.09.14.507916

Cryo-EM-based structural insights into supramolecular assemblies of γ-Hemolysin from Staphylococcus aureus reveal the pore formation mechanism.

Mishra, S.·Roy, A. K.·Dutta, S.
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Abstract

{gamma}-hemolysin ({gamma}-HL) is a hemolytic and leukotoxic bicomponent {beta}-pore-forming toxin ({beta}-PFT), a potent virulence factor from Staphylococcus aureus Newman strain. In this study, we performed single particle cryo-EM of {gamma}-HL in a lipid environment. We observed clustering and square lattice packing of octameric HlgAB pores upon membrane bilayer, and an octahedral superassembly of octameric pore complexes, that we resolved at resolution 3.5 [A]. Our atomic model further demonstrated the key residues involved in hydrophobic zipping between the rim domains of adjacent octameric pore complexes, thus providing first evidence of additional structural stability in PFTs upon membrane lysis. We also observed lipid densities at the octahedral and octameric interfaces, providing critical insights into the lipid-binding residues involved for both HlgA and HlgB components. Furthermore, the hitherto elusive N-terminal region of HlgA has also been resolved in our cryo-EM map and an overall mechanism of pore formation for bicomponent {beta}-PFTs is proposed.

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Mishra, S., Roy, A. K., Dutta, S.. 2022-09-15. Cryo-EM-based structural insights into supramolecular assemblies of γ-Hemolysin from Staphylococcus aureus reveal the pore formation mechanism.. https://doi.org/10.1101/2022.09.14.507916

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