Monastrol stabilises an attached low-friction mode of Eg5

Monastrol [1] is a small molecule that inhibits a mitotic kinesin called Eg5. In cells, monastrol dramatically arrests mitosis with a defect in the engagement and relative sliding of the two half-spindles [1,2]. We show here that monastrol stabilises a remarkable low-friction attached mode of Eg5 that binds stably to microtubules, yet can be readily slid along them. We will suggest that this mode is part of the normal Eg5 kinetic cycle ('on-pathway'), with significant consequences for the in vivo role of Eg5 and for the interpretation of experiments involving monastrol.