Torque Generation of Kinesin Motors Is Governed by the Stability of the Neck Domain

SummaryIn long-range transport of cargo, prototypical kinesin-1 steps along a single protofilament on the microtubule, an astonishing behavior given the number of theoretically available binding sites on adjacent protofilaments. Using a laser trap assay, we analyzed the trajectories of several representatives from the kinesin-2 class on freely suspended microtubules. In stark contrast to kinesin-1, these motors display a wide range of left-handed spiraling around microtubules and thus generate torque during cargo transport. We provide direct evidence that kinesin's neck region determines the torque-generating properties. A model system based on kinesin-1 corroborates this result: disrupting the stability of the neck by inserting flexible peptide stretches resulted in pronounced left-handed spiraling. Mimicking neck stability by crosslinking significantly reduced the spiraling of the motor up to the point of protofilament tracking. Finally, we present a model that explains the physical basis of kinesin's spiraling around the microtubule.

Graphical AbstractFigure optionsDownload high-quality image (218 K)Download as PowerPoint slideHighlights
► Trajectories of kinesins on suspended microtubules are analyzed
► Kinesin-2 motors display a broad range of spiraling around microtubules
► The stability of the neck region is the molecular determinant of spiraling