Computational Modeling Reveals a Catch-and-Guide Interaction Between Kinesin-1 and Tubulin C-Terminal Tails

The delivery of intracellular cargoes by kinesins is modulated at scales ranging from the geometry of the microtubule networks down to interactions with individual tubulins and their code. The complexity of the tubulin code and the difficulty in directly observing motor-tubulin interactions have hindered progress in pinpointing the precise mechanisms by which kinesin's function is modulated. As one such example, past experiments show that cleaving tubulin C-terminal tails (CTTs) lowers kinesin-1's processivity and velocity on microtubules, but how these CTTs intertwine with kinesin's processive cycle remains unclear. In this work, we formulate and interrogate several plausible mechanisms by which CTTs contribute to and modulate kinesin motion. Computational modeling bridges the gap between effective transport observations (processivity, velocities) and microscopic mechanisms. Ultimately, we find that a guiding mechanism can best explain the observed differences in processivity and velocity. Altogether, our work adds a new understanding of how the CTTs and their modulation via the tubulin code may steer intracellular traffic in both health and disease.