Sequence and Functional Diversity Across the Kinesin Superfamily

Abstract

Members of the kinesin superfamily are defined by the presence a kinesin motor domain containing signature sequences for nucleotide and microtubule binding. A variety of biochemical and biophysical studies of the core kinesin-1 motor domain have illuminated how nucleotide binding and hydrolysis lead to force generation and motility along microtubules. Alternating catalysis by the two motor domains enables processive motility along the microtubule surface. It has been assumed that this is the mechanistic paradigm for all kinesin motors. However, recent work indicates that sequence divergence within the kinesin motor domain endows different kinesin motors with distinct microtubule-based properties. We examined how evolutionary tuning of the core motor domain endowed kinesin-3 motors with a high microtubule on-rate, high velocity, and superprocessivity. We also examined sequence divergence within the kinesin-4 family of motors such that some members of this family lost the ability to undergo processive motility.