ArticleThe Journal of biological chemistry2015
Structure-function analysis of heterodimer formation, oligomerization, and receptor binding of the Staphylococcus aureus bi-component toxin LukGH.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 60 citations in OpenAlex.
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- Functional and Proteomic Dissection of the Contributions of CodY, SigB and the Hibernation Promoting Factor HPF to Interactions ofJournal of proteome research · 2024Article
- The Relative Importance of Cytotoxins Produced by Methicillin-ResistantMicroorganisms · 2024Article
- Overview of Bacterial Protein Toxins from Pathogenic Bacteria: Mode of Action and Insights into Evolution.Toxins · 2024Review
- Molecular Characteristics and Pathogenicity ofInternational journal of molecular sciences · 2023Review
- Gating of β-Barrel Protein Pores, Porins, and Channels: An Old Problem with New Facets.International journal of molecular sciences · 2023Review
- Bacterial pore-forming toxins.Microbiology (Reading, England) · 2022Article
- Genetic variation of staphylococcal LukAB toxin determines receptor tropism.Nature microbiology · 2021Article
- Review
- Structure-based discovery of a small-molecule inhibitor of methicillin-resistantThe Journal of biological chemistry · 2020Article
- Unbiased Identification of Immunogenic Staphylococcus aureus Leukotoxin B-Cell Epitopes.Infection and immunity · 2020Article
- Molecular mechanism of leukocidin GH-integrin CD11b/CD18 recognition and species specificity.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Rational Design of Toxoid Vaccine Candidates forToxins · 2019Article
- Review
- Inhibition of bacterial toxin recognition of membrane components as an anti-virulence strategy.Journal of biological engineering · 2019Review
- Article
- Review
- Disarming Staphylococcus aureus from destroying human cells by simultaneously neutralizing six cytotoxins with two human monoclonal antibodies.Virulence · 2018Article
- Staphylococcus aureus pore-forming toxins: The interface of pathogen and host complexity.Seminars in cell & developmental biology · 2017Review
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The bi-component leukocidins of Staphylococcus aureus are important virulence factors that lyse human phagocytic cells and contribute to immune evasion. The γ-hemolysins (HlgAB and HlgCB) and Panton-Valentine leukocidin (PVL or LukSF) were shown to assemble from soluble subunits into membrane-bound oligomers on the surface of target cells, creating barrel-like pore structures that lead to cell lysis. LukGH is the most distantly related member of this toxin family, sharing only 30-40% amino acid sequence identity with the others. We observed that, unlike other leukocidin subunits, recombinant LukH and LukG had low solubility and were unable to bind to target cells, unless both components were present. Using biolayer interferometry and intrinsic tryptophan fluorescence we detected binding of LukH to LukG in solution with an affinity in the low nanomolar range and dynamic light scattering measurements confirmed formation of a heterodimer. We elucidated the structure of LukGH by x-ray crystallography at 2.8-Å resolution. This revealed an octameric structure that strongly resembles that reported for HlgAB, but with important structural differences. Structure guided mutagenesis studies demonstrated that three salt bridges, not found in other bi-component leukocidins, are essential for dimer formation in solution and receptor binding. We detected weak binding of LukH, but not LukG, to the cellular receptor CD11b by biolayer interferometry, suggesting that in common with other members of this toxin family, the S-component has the primary contact role with the receptor. These new insights provide the basis for novel strategies to counteract this powerful toxin and Staphylococcus aureus pathogenesis.
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