2005/08/16 by Daniel W. Schuerch, Elizabeth M. Wilson-Kubalek, Rodney K. Tweten · 2 citations
Biochemistry, Genetics and Molecular Biology · #Listeria monocytogenes in Food Safety #Microbial Inactivation Methods #Viral Infectious Diseases and Gene Expression in Insects
paper · doi:10.1073/pnas.0500558102
openalex publication_date 2005/08/16 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
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.