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

View ORCID ProfileSuman Mishra, View ORCID ProfileAnupam Roy, View ORCID ProfileSomnath Dutta
doi: https://doi.org/10.1101/2022.09.14.507916
Suman Mishra
1Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560012, India
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Anupam Roy
1Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560012, India
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Somnath Dutta
1Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560012, India
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  • For correspondence: somnath@iisc.ac.in
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ABSTRACT

γ-hemolysin (γ-HL) is a hemolytic and leukotoxic bicomponent β-pore-forming toxin (β-PFT), a potent virulence factor from Staphylococcus aureus Newman strain. In this study, we performed single particle cryo-EM of γ-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 Å. 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 β-PFTs is proposed.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted September 15, 2022.
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Cryo-EM-based structural insights into supramolecular assemblies of γ-Hemolysin from Staphylococcus aureus reveal the pore formation mechanism
Suman Mishra, Anupam Roy, Somnath Dutta
bioRxiv 2022.09.14.507916; doi: https://doi.org/10.1101/2022.09.14.507916
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Cryo-EM-based structural insights into supramolecular assemblies of γ-Hemolysin from Staphylococcus aureus reveal the pore formation mechanism
Suman Mishra, Anupam Roy, Somnath Dutta
bioRxiv 2022.09.14.507916; doi: https://doi.org/10.1101/2022.09.14.507916

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