Proceedings of the National Academy of Sciences - PNAS, 2005-08, Vol.102 (35), p.12537-12542
2005
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- Autor(en) / Beteiligte
- Titel
- Molecular Basis of Listeriolysin O pH Dependence
- Ist Teil von
- Proceedings of the National Academy of Sciences - PNAS, 2005-08, Vol.102 (35), p.12537-12542
- Ort / Verlag
- United States: National Academy of Sciences
- Erscheinungsjahr
- 2005
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Listeriolysin O (LLO) is a cholesterol-dependent cytolysin that is an essential virulence factor of Listeria monocytogenes. LLO pore-forming activity is pH-dependent; it is active at acidic pH (<6), but not an neutral pH. In contrast to other pH-dependent toxins, we have determined that LLO pore-forming activity is controlled by a rapid and irreversible denaturation of its structure at neutral pH at temperatures > 30°C. Rapid denaturation is triggered at neutral pH by the premature unfolding of the domain 3 transmembrane β-hairpins; structures that normally form the transmembrane β-barrel. A triad of acidic residues within domain 3 function as the pH sensor and initiate the denaturation of LLO by destabilizing the structure of domain 3. These studies provide a view of a molecular mechanism by which the activity of a bacterial toxin is regulated by pH.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0027-8424eISSN: 1091-6490DOI: 10.1073/pnas.0500558102Titel-ID: cdi_proquest_journals_201298397
- Format
- –
- Schlagworte
- Aggregation, Bacteria, Bacterial Toxins - chemistry, Bacterial Toxins - genetics, Bacterial Toxins - toxicity, Biological Sciences, Carboxylates, Disulfides, Fluorescence, Genes, Bacterial, Heat-Shock Proteins - chemistry, Heat-Shock Proteins - genetics, Heat-Shock Proteins - toxicity, Heat-Shock Proteins - ultrastructure, Hemolysin Proteins, Hemolysis, Hemolysis - drug effects, Humans, Hydrogen-Ion Concentration, In Vitro Techniques, Listeria monocytogenes, Listeria monocytogenes - chemistry, Listeria monocytogenes - genetics, Listeria monocytogenes - pathogenicity, Microbiology, Microscopy, Electron, Models, Molecular, Molecular biology, Monomers, Multiprotein Complexes, Phagosomes, Point Mutation, Protein Conformation, Protein Denaturation, Protein Structure, Tertiary, Recombinant Proteins - chemistry, Recombinant Proteins - genetics, Recombinant Proteins - toxicity, Recombinant Proteins - ultrastructure, Sensors, Spectrometry, Fluorescence, Temperature, Toxins