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  • Sterol and pH interdependence in the binding, oligomerization, and pore formation of listeriolysin O
    Bavdek, Andrej ...
    Listeriolysin O (LLO) is the most important virulence factor of the intracellular pathogen Listeria monocytogerzes. Its main task is to enable escape of bacteria from the phagosomal vacuole into the ... cytoplasm. LLO belongsto the cholesterol-dependent cytolysis (CDC) family but differs from other members, as it exhibits optimal activity at low pH. Its pore forming ability at higher pH values has been largely disregarded in Listeria pathogenesis. Here we show that High cholesterol concentrations in the membrane restore the low activity of LLO at high pH values. LLO binds to lipidmembranes, at physiological or even slightly basic pH values, in a cholesterol-dependent fashion. Binding, insertion into lipid monolayers, and permeabilization of calcein-loaded liposomes are maximal above approximately 35 mol % cholesterol, a concentration range typically found in lipid rafts. The narrow transition region of cholesterol concentration separating low and high activity indicates that cholesterol not only allows the binding of LLO tomembranes but also affects other steps in pore formation. We were able to detect some of these by surface plasmon resonance-based assays. In particular,we show that LLO recognition of cholesterol is determined by the most exposed 3% beta-hydroxy group of cholesterol. In addition, LLO binds and permeabilizes J774 cells and human erythrocytes in a cholesterol-dependent fashion at physiological or slightly basic pH values. Tle results clearly showthat LLO activity at physiological pH cannot be neglected and that its action at sites distal to cell entry may have important physiological consequences for Listeria pathogenesis.
    Vir: Biochemistry. - ISSN 0006-2960 (Letn. 46, št. 14, 2007, str. 4425-4437)
    Vrsta gradiva - članek, sestavni del
    Leto - 2007
    Jezik - angleški
    COBISS.SI-ID - 22569689

vir: Biochemistry. - ISSN 0006-2960 (Letn. 46, št. 14, 2007, str. 4425-4437)
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