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Kinesin follows the microtubule's protofilament axis

S Ray1, E Meyhöfer, R A Milligan

  • 1Department of Physiology and Biophysics, University of Washington, Seattle 98195.

Insights

Kinesin motors move along microtubules by following protofilament paths. This precise movement dictates specific spacing between kinesin-binding sites on the microtubule structure.

Area of Science:

  • Cellular biology
  • Biophysics
  • Molecular motors

Background:

  • Kinesin is a motor protein that transports cargo within cells along microtubule tracks.
  • The precise path kinesin takes along microtubules is crucial for understanding intracellular transport mechanisms.
  • Microtubules are composed of protofilaments, whose arrangement can influence motor protein movement.

Purpose of the Study:

  • To test the hypothesis that kinesin moves parallel to the microtubule's protofilament axis.
  • To determine if microtubule protofilament structure dictates kinesin's movement path.
  • To investigate the implications of kinesin's path for kinesin-binding site spacing.

Main Methods:

  • Polymerization of microtubules with distinct protofilament orientations (parallel vs. helical).
  • Observing microtubule gliding on kinesin-coated surfaces.
  • Measuring microtubule rotation, pitch, and handedness using electron cryo-microscopy.
  • Analyzing the relationship between protofilament supertwist and observed rotation.

Main Results:

  • Microtubules with parallel protofilaments did not rotate when gliding on kinesin.
  • Microtubules with helical (supertwisted) protofilaments exhibited rotation.
  • The observed rotation pitch and handedness correlated with the protofilament supertwist.
  • Kinesin demonstrated high-fidelity movement along the protofilament axis.

Conclusions:

  • Kinesin motor proteins move with high fidelity along the microtubule protofilament axis.
  • This precise movement implies that kinesin-binding sites on microtubules are spaced at integral multiples of 4.1 nm or 8.2 nm.
  • The findings provide critical insights into the molecular mechanism of kinesin-microtubule interaction.

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