21 Mar 2024

Myosin-5 carries cargoes inside cells by walking along helical F-actin filaments. Myosin-5 avoids walking helically by taking long steps equal to F-actin’s helical repeat. Previous measurements of step length show a broader spread of values than expected from the spatial resolution of the technique. We used iSCAT and electron microscopies, which have subnanometer precision, and find that the broad peak is really a family of narrow peaks that correspond to steps spanning different numbers of subunits along F-actin. We show that disorder within F-actin is the reason myosin-5 varies its step length because the F-actin subunit best oriented for walking in a straight line changes from step to step. Thus F-actin disorder has important impacts on cellular functions. This paper is the outcome of a longstanding collaboration between the Kukura group and NIH in Bethesda.