Preprint Highlight: Kinesin-binding protein remodels the kinesin motor to prevent microtubule binding

Abstract

Kinesin-binding protein (KIFBP) interacts with a subset of 8 of the 45 human kinesin family members and prevents their binding to microtubules, yet it was unclear how KIFBP selectively binds to this subset. By combining cryoelectron microscopy and cross-linking mass spectrometry, it was revealed that KIFBP uses a multivalent interaction to bind to at least two different kinesins, Kif18a and Kif15. This confirms a recent study of Kif15, extends the structural analysis to Kif18a, and uses molecular dynamics simulations to suggest KIFBP selectivity is determined by whether a kinesin loop prefers secondary structure or disorder. This work will be important to researchers studying molecular motors and structural biologists because it reveals uncommon mechanisms for molecular interaction.