What planar lipid membranes tell us about the pore-forming activity of cholesterol-dependent cytolysins

Abstract

Pore-forming toxins are an important group of natural molecules that damage cellular membranes by forming transmembrane pores. They are used by many organisms for attack or defense and similar proteins are employed in the immune system of vertebrates. Various biophysical approaches have been used to understand how these proteins act at the molecular level. One of the most useful, in terms of monitoring pore formation in real time, is a method that employs planar lipid membranes and involves ionic current measurements. Here we highlight the advantages and possibilities that this approach offers and show how it can advance understanding of the pore-forming mechanism and pore properties for one of the most important families of natural toxins, the cholesterol-dependent cytolysins.

Keywords: 1,2-dioleoyl-sn-glycero-3-phosphocholine; 1,2-diphytanoyl-sn-glycero-3-phosphocholine; 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine; 2-(N-morpholino)ethanesulfonic acid; AFM; CDC; Chol; Cholesterol-dependent cytolysin; D; DOPC; DPhPC; Hepes; LLO; Listeriolysin O; MES; N-2-hydroxyethylpiperazine-N′-2-ethanesulphonic acid; PC; PFO; PFT; PLM; PLY; POPC; Perfringolysin O; Planar lipid membranes; Pore; Pore-forming toxin; TMH; Tris; atomic force microscopy; cholesterol; cholesterol-dependent cytolysins; domain; listeriolysin O; perfringolysin O; phosphatidylcholine; planar lipid membrane; pneumolysin; pore-forming toxin; transmembrane β-hairpin; tris(hydroxymethyl)aminomethane.