The mechanochemical output of the kinesin-2 motor kif3ac is tuned by heterodimerization

Abstract

The kinesin-2 family of molecular motors is unusual among kinesins in that it contains both hetero- and homodimeric motors. It is of importance to understand the impact and purpose of heterodimerization in the kinesin-2 family. Mammals express two kinesin-2 heterodimers, KIF3AB and KIF3AC, resulting from 3 genes, kif3a, kif3b, and kif3c, as well as homodimeric KIF17 from the kif17 gene. KIF3AC is of particular interest because KIFA and KIF3C have a 30-fold difference in velocity when expressed as engineered homodimers. The work presented here seeks to define the potential transport capabilities of KIF3AC. This was accomplished by optical trapping techniques and iSCAT (interferometric scattering) microscopy in order to define the behavior of these distinct motor domains during a processive run. The results show that KIF3AC is strikingly more sensitive to external load than KIF3AB, and that KIF3AC steps are characterized by a single observed rate constant and not two independent rate constants as one may expect for fast KIF3A and slow KIF3C. Together, these results suggest that it is unlikely that KIF3AC can transport cargo as one or a few motors and that the KIF3AC heterodimer shows an emergent mechanochemistry in which KIF3A is slowed and KIF3C is accelerated. I argue that this change in kinetics is mediated by interhead tension.