Kinesin's structure includes a cargo-binding domain, a long stalk, and a pair of motor heads, which move along microtubules mostly hand over hand. Each motor head is connected to the stalk by a short neck linker. The neck linker has been suggested to help kinesin motility by making a large, ATP-driven conformational change that docks it to the motor head and results in a forward-stepping motion. But an unbound neck linker is flexible and interacts only weakly with the motor head; thus, it alone cannot generate the required force. The authors now discover an additional mechanical element not previously implicated in kinesin motility—the cover strand, which dangles nearby.
When ATP binds to the motor head, the cover strand and the neck linker form a new β-sheet domain, which the authors named the cover neck bundle. The bundle pushes the neck linker into its binding pocket, where it then latches on, powering the free motor head forward. Force analysis indicated that forces generated by the cover neck bundle agreed with experimental measurements.
“The force is generated by the formation of this domain rather than by switching between well-defined conformations,” Hwang says. “It was not possible to obtain these results from structural studies only, since it's a dynamic structure.”