Mechano-Chemical Model for the Mechanism of Directed Processive Motility of Cytoplasmic Dynein

Abstract

Linear motor proteins move along their tracks by performing a mechano-chemical cycle in which the conformational and binding affinity changes are coupled to the ATP hydrolysis cycle. Although the two way coupling between the catalytic site, track binding and lever motion is a universal feature of myosins, kinesins and dyneins, the experiments on mutants with one inactive motor head suggest that the dimeric motor could be functional with a less complex mechanism. In this talk we will discuss the minimal prerequisites for the dimeric motor to move processively in a directed fashion. Without any coupling between the catalytic site and binding domain, asymmetric unbinding of the trail/lead head and/or asymmetric binding in the forward/backward direction can be driven solely by an asymmetry in the force-induced unbinding rate, together with a conformation dependent internal tension of the dimeric motor. However, the stepping efficiency of such motility is much lower than that of a motor with further allosteric coupling. A more specific and complex mechano-chemical model for cytoplasmic dynein reproduces well the observed stepping efficiency, velocity and force production. By changing the strength of the interhead elastic interaction the model accounts both for uncoordinated and coordinated stepping characteristics of yeast and mammalian dyneins, as observed in recent single-molecule studies.