Work

Molecular basis of listeriolysin O pH dependence

Year: 2005

Type: article

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.

Source: Proceedings of the National Academy of Sciences

DOI: 10.1073/pnas.0500558102

Authors: Daniel W. Schuerch, Elizabeth M. Wilson-Kubalek, Rodney K. Tweten

Institutions: Scripps Research Institute, University of Oklahoma Health Sciences Center

Language: English

Topic: Bacterial Genetics and Biotechnology

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

Funder: National Institute of Allergy and Infectious Diseases

Award: Pore Formation by Cholesterol Dependent Cytolysins