PMID:16105950
| Citation |
Schuerch, DW, Wilson-Kubalek, EM and Tweten, RK (2005) Molecular basis of listeriolysin O pH dependence. Proc. Natl. Acad. Sci. U.S.A. 102:12537-42 |
|---|---|
| Abstract |
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 at 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 degrees C. Rapid denaturation is triggered at neutral pH by the premature unfolding of the domain 3 transmembrane beta-hairpins; structures that normally form the transmembrane beta-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. |
| Links |
PubMed PMC1194900 Online version:10.1073/pnas.0500558102 |
| Keywords |
Bacterial Toxins/chemistry; Bacterial Toxins/genetics; Bacterial Toxins/toxicity; Genes, Bacterial; Heat-Shock Proteins/chemistry; Heat-Shock Proteins/genetics; Heat-Shock Proteins/toxicity; Heat-Shock Proteins/ultrastructure; Hemolysin Proteins; Hemolysis/drug effects; Humans; Hydrogen-Ion Concentration; Listeria monocytogenes/chemistry; Listeria monocytogenes/genetics; Listeria monocytogenes/pathogenicity; Microscopy, Electron; Models, Molecular; Multiprotein Complexes; Point Mutation; Protein Conformation; Protein Denaturation; Protein Structure, Tertiary; Recombinant Proteins/chemistry; Recombinant Proteins/genetics; Recombinant Proteins/toxicity; Recombinant Proteins/ultrastructure; Spectrometry, Fluorescence; Temperature |
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