Directional Stepping Model for Yeast Dynein: Longitudinal- and Side-Step Distributions

Biophys J. 2019 Nov 19;117(10):1892-1899. doi: 10.1016/j.bpj.2019.09.043. Epub 2019 Oct 10.

Abstract

Motor proteins are biological machines that convert chemical energy stored in ATP to mechanical work. Kinesin and dynein are microtubule (MT)-associated motor proteins that, among other functions, facilitate intracellular transport. Here, we focus on dynein motility. We deduce the directional step distribution of yeast dynein motor protein on the MT surface by combing intrinsic features of the dynein and MTs. These include the probability distribution of the separation vector between the two microtubule-binding domains, the angular probability distribution of a single microtubule-binding domain translation, the existence of an MT seam defect, MT-binding sites, and theoretical extension that accounts for a load force on the motor. Our predictions are in excellent accord with the measured longitudinal step size distributions at various load forces. Moreover, we predict the side-step distribution and its dependence on longitudinal load forces, which shows a few surprising features. First, the distribution is broad. Second, in the absence of load, we find a small right-handed bias. Third, the side-step bias is susceptible to the longitudinal load force; it vanishes at a load equal to the motor stalling force and changes to a left-hand bias above that value. Fourth, our results are sensitive to the ability of the motor to explore the seam several times during its walk. Although available measurements of side-way distribution are limited, our findings are amenable to experimental check and, moreover, suggest a diversity of results depending on whether the MT seam is viable to motor sampling.

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Binding Sites
  • Biomechanical Phenomena
  • Dyneins / chemistry
  • Dyneins / metabolism*
  • Models, Biological*
  • Probability
  • Protein Binding
  • Protein Domains
  • Saccharomyces cerevisiae / metabolism*
  • Temperature

Substances

  • Adenosine Triphosphate
  • Dyneins