Mechanical unfolding of bacterial flagellar filament protein by molecular dynamics simulation

Bacterial flagellum is a nano-scale motility device constructed by self-assembly. During construction of the cell-exterior filament (the 'propeller'), subunit proteins (called flagellin) are thought to be exported through the hollow flagellum to the growing filament tip in an unfolded state. To gain insight into the unfolded state preceding any force-spectroscopy experiments on flagellin, we employed force-probe molecular dynamics simulations. Two schemes to attain an unfolded state suitable for efficient transport were examined: (i) stretching flagellin along its length; (ii) unzipping flagellin from its adjacently placed termini. Atomic-level unfolding pathways and the mechanical efforts involved under each scheme were obtained for the four-domain flagellin from S. typhimurium. Flagellin appeared stiffer and required larger unfolding forces when stretched as the relative sliding of beta-strands require the breaking of multiple hydrogen bonds at once. In contrast, unzipping requires lower unfolding forces as it mainly involves unraveling beta-sheets by breaking hydrogen bonds one by one.