Mapping the Processivity Determinants of the Kinesin-3 Motor Domain

Biophys J. 2015 Oct 20;109(8):1537-40. doi: 10.1016/j.bpj.2015.08.027.


Kinesin superfamily members play important roles in many diverse cellular processes, including cell motility, cell division, intracellular transport, and regulation of the microtubule cytoskeleton. How the properties of the family-defining motor domain of distinct kinesins are tailored to their different cellular roles remains largely unknown. Here, we employed molecular-dynamics simulations coupled with energetic calculations to infer the family-specific interactions of kinesin-1 and kinesin-3 motor domains with microtubules in different nucleotide states. We then used experimental mutagenesis and single-molecule motility assays to further assess the predicted residue-wise determinants of distinct kinesin-microtubule binding properties. Collectively, our results identify residues in the L8, L11, and α6 regions that contribute to family-specific microtubule interactions and whose mutation affects motor-microtubule complex stability and processive motility (the ability of an individual motor to take multiple steps along its microtubule filament). In particular, substitutions of prominent kinesin-3 residues with those found in kinesin-1, namely, R167S/H171D, K266D, and R346M, were found to decrease kinesin-3 processivity 10-fold and thus approach kinesin-1 levels.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Kinesins / chemistry*
  • Kinesins / genetics
  • Kinesins / metabolism*
  • Microtubules / metabolism*
  • Molecular Dynamics Simulation
  • Mutagenesis
  • Mutation
  • Protein Interaction Domains and Motifs
  • Tubulin / metabolism


  • Tubulin
  • Kinesins