What are backward myosins?

Answer 1

Myosin VI attracted attention as a candidate for a (−)-end-directed motor after the identification of a class-specific insert following the converter domain. In the swinging cross-bridge model of actomyosin function, the converter domain transmits motion from the myosin head to the C-terminal lever arm, generating a directed power stroke. Wells et al. (3) hypothesized that a structure inserted between the converter domain and the lever arm could redirect the stroke and lead to backward movement. The predicted reverse directionality of myosin VI was experimentally confirmed (3), but the precise mechanism of this remarkable adaptation remained unclear, including whether the unique insert was necessary and sufficient for stroke reversal.

Tsiavaliaris et al. (6) used protein engineering to show that the proposed mechanism of power stroke reversal was feasible. They inserted a four-helix bundle after the converter domain of a (+)-end-directed myosin, redirecting the lever arm by 180° and generating an artificial (−)-end-directed motor. Their results clearly demonstrate that an insertion between the converter domain and the lever arm can be sufficient for directionality reversal in a myosin, but leave open the question of whether myosin VI takes advantage of this available mechanism.

Homma et al. (7) questioned whether the unique insert was necessary for directionality reversal. They characterized a collection of chimeric motors in which portions of myosin VI were fused to portions of myosin V, with surprising results. One chimera contained the motor domain of myosin VI (including the converter but not the subsequent unique insert) fused to the lever arm of myosin V. This construct was reported to generate (−)-end-directed motion, suggesting that the determinants of directionality might be located within the motor domain.

Answer 2

Backward myosins are a type of motor protein that move toward the minus end of actin filaments, in the opposite direction of most myosins. They play a role in various cellular processes such as cytokinesis and organelle transport.