Pore Forming Protein Induced Biomembrane Reorganization and Dynamics: A Focused Review

Pore forming proteins are a broad class of pathogenic secreted by organisms as virulence factors due to their ability form pores on the target cell membrane. Bacterial pore toxins (PFTs) belong subclass widely implicated in bacterial infections. Although action PFTs cells have been investigated, underlying membrane response lipids during binding and formation has received less attention. With advent superresolution microscopy well carry out molecular dynamics (MD) simulations large protein assemblies, novel microscopic insights mechanism emerged over last decade. In this review, we focus primarily results collated our laboratory which probe dynamic lipid reorganization induced plasma various stages two archetypal PFTs, cytolysin A (ClyA), an α -toxin listeriolysin O (LLO), β -toxin. The extent perturbation is dependent both secondary structure inserted motifs complex topological variations complex. Using confocal stimulated emission depletion (STED) fluorescence correlation spectroscopy (FCS) MD simulations, diffusion, cholesterol deviations from Brownian diffusion correlated with oligomeric state bound composition. Deviations free typically observed at length scales below ∼130 nm reveal presence local dynamical heterogeneities that emerge nanoscale—driven part preferential domains present Interrogating nanoscale allows us further differentiate between - -PFTs specific gained intricate coupling occurs receptors expected improve understanding virulent PFTs.