Myosin-V makes two brownian 90 degrees rotations per 36-nm step.

Myosin-V processively walks on actin filaments in a hand-over-hand fashion. The identical structures of the heads predict a symmetric hand-over-hand mechanism where regular, unidirectional rotation occurs during a 36-nm step. We investigated this by observing how fixed myosin-V rotates actin filaments. Actin filaments randomly rotated 90 degrees both clockwise and counter-clockwise during each step. Furthermore, ATP-dependent rotations were regularly followed by ATP-independent ones. Kinetic analysis indicated that the two 90 degrees rotations relate to the coordinated unbinding and rebinding of the heads with actin. We propose a 'brownian rotation hand-over-hand' model, in which myosin-V randomly rotates by thermally twisting its elastic neck domains during the 36-nm step. The brownian rotation may be advantageous for cargo transport through a crowded actin meshwork and for carrying cargoes reliably via multiple myosin-V molecules in the cell.