Muscle motor shifts into reverse

Engineered motor protein holds nanotechnological promise.

Myosin is the motor protein that moves along actin filaments and thereby powers our muscles. Apart from one unexplained exception, all known myosins move in the same direction, namely towards the barbed (+) end of the actin strand. Now Dietmar Manstein’s group in Hannover, Germany, has succeeded in engineering a myosin variant that moves in the opposite direction.

The key functional element in myosin is the hinge between the ATP-fuelled motor domain and the fibrillar part of the molecule that is normally anchored in the thick filament of the muscle. During the power stroke, the motor domain moves by rotating its relative position to the filament around this hinge. There is currently no obvious way by which molecular engineers could persuade the motor domain to rotate the other way round. But there are ways of replacing the filamentous part of myosin, which essentially acts as a lever, with other molecular building blocks.

In their previous work, Manstein and coworkers engineered myosin variants with artificial lever arms. ¹ Building on that experience, they have now attached a U-shaped lever to the hinge. They suspected that, with the lever end pointing in the opposite direction, the rotation on the hinge would translate into reverse gear translational motion. To test the prediction experimentally, the researchers attached the myosin construct to a solid support and allowed it to shift around actin filaments which were labelled with green fluorescence at the (-) end and with red fluorescence along the filament. ² As one might predict, natural myosin and the previous construct made the red worm follow the green tip, while the U-turn construct made the actin move in the opposite direction, with the green light trailing. With different points of attachment (on either side of the U-turn) one could even use the same construct for both directions.

For the future of engineering molecular motors to fit nanotechnology devices, this achievement is just a beginning. Using the same approach, says Manstein, ’other or more building blocks derived from unrelated proteins can be used to engineer new activities and features, like the potential for self-assembly, into the recombinant motors’.

Michael Gross