Abstract
ABSTRACTγ-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.
Publisher
Cold Spring Harbor Laboratory
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献