Direct observation of the binding state of the kinesin head to the microtubule

Nature. 2009 Sep 3;461(7260):125-8. doi: 10.1038/nature08259. Epub 2009 Aug 19.

Abstract

The dimeric motor protein kinesin-1 converts chemical energy from ATP hydrolysis into mechanical work used to transport cargo along microtubules. Cargo attached to the kinesin stalk moves processively in 8-nm increments as its twin motor domains (heads) carry out an asymmetric, 'hand-over-hand' walk. The extent of individual head interactions with the microtubule during stepping, however, remains controversial. A major experimental limitation has been the lack of a means to monitor the attachment of an individual head to the microtubule during movement, necessitating indirect approaches. Here we report the development of a single-molecule assay that can directly report head binding in a walking kinesin molecule, and show that only a single head is bound to the microtubule between steps at low ATP concentrations. A bead was linked to one of the two kinesin heads by means of a short DNA tether and used to apply rapidly alternating hindering and assisting loads with an optical trap. The time-dependent difference between forwards and backwards displacements of the bead alternated between two discrete values during stepping, corresponding to those intervals when the linked head adopted a bound or an unbound state. The linked head could only rebind the microtubule once ATP had become bound to its partner head.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Adenosine Triphosphate / pharmacology
  • Animals
  • DNA / chemistry
  • DNA / metabolism
  • Drosophila melanogaster
  • Kinesins / chemistry*
  • Kinesins / metabolism*
  • Microspheres
  • Microtubules / metabolism*
  • Movement / drug effects
  • Optical Tweezers
  • Protein Binding / drug effects
  • Time Factors

Substances

  • Adenosine Triphosphate
  • DNA
  • Kinesins