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

Mishra, S and Roy, A and Dutta, S (2023) Cryo-EM-based structural insights into supramolecular assemblies of γ-hemolysin from S. aureus reveal the pore formation mechanism. In: Structure, 31 (6). 651-667.e5.

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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 the Staphylococcus aureus Newman strain. In this study, we performed single-particle cryoelectron microscopy (cryo-EM) of γ-HL in a lipid environment. We observed clustering and square lattice packing of octameric HlgAB pores on the membrane bilayer and an octahedral superassembly of octameric pore complexes that we resolved at resolution of 3.5 Å. Our atomic model further demonstrated the key residues involved in hydrophobic zipping between the rim domains of adjacent octameric complexes, providing additional structural stability in PFTs post oligomerization. We also observed extra densities at the octahedral and octameric interfaces, providing insights into the plausible lipid-binding residues involved for HlgA and HlgB components. Furthermore, the hitherto elusive N-terminal region of HlgA was also resolved in our cryo-EM map, and an overall mechanism of pore formation for bicomponent β-PFTs is proposed. © 2023 Elsevier Ltd

Item Type:	Journal Article
Publication:	Structure
Publisher:	Cell Press
Additional Information:	The copyright of this article belongs to Cell Press
Department/Centre:	Division of Biological Sciences > Molecular Biophysics Unit
Date Deposited:	14 Jun 2023 11:10
Last Modified:	14 Jun 2023 11:10
URI:	https://eprints.iisc.ac.in/id/eprint/81891

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