A structure-based sequential mechano-chemical model of hexameric helicases

From accumulating studies of hexameric helicases, a mechano-chemical coupling mechanism has emerged which postulates that the nucleoside: triphosphate (NTP) hydrolysis is sequentially coordinated together with the binding and translocation of nucleic acid substrate. Various mechano-chemical models have been proposed for different hexameric helicases with no consensus for a common mechanism. To explain both conserved and variable features of the mechano-chemical coupling in various hexameric helicases, we propose a tri-site sequential model for NTP hydrolysis and substrate translocation It builds upon structurally derived coupling rules that map the chemical state of a nucleotide-binding site to the longitudinal positions of the substrate-binding loops in two adjoined subunits. The coupling rules symbolize the mechano-chemical couplings via both the trans- and cis-residues of a nucleotide-binding site, and facilitate sequentially coordinated hydrolysis involving three consecutive nucleotide-binding sites at one time. Four schemes exist within our model, which differ in hydrolysis direction and substrate-binding mode. By applying our general model to five hexameric helicases (Rho, T7, P4, E1 and LTag) we have predicted various mechano-chemical properties of these NTPase-based motors (including hydrolysis direction, NTP-binding cooperativity, substrate-binding mode, translocation direction and step size, force-generation step). These predictions agree with past experimental data and call for future experimental test.