How does kinesin-1 move processively along the microtubule? Alternative binding of the two heads is thought to involve "gating" of the ATPase cycles of each head to coordinate their binding and release. The mechanism by which gating occurs is not certain. New data show that, unexpectedly, kinesin-1 can bind tubulin dimers, causing release of ADP. The work reveals a nucleotide-dependent release of a block on the tethered head that operates independently of the microtubule lattice.
Alonso, M. C., Drummond, D. R., Kain, S., Honeng, J., Amos, L. & Cross, R. A. 2007. An ATP gate controls tubulin binding by the tethered head of kinesin-1. Science 316, 20-123.
Kinesin-14 Structure
The kinesin-14 motor, Kar3, exists as a heterodimer with a nonmotor subunit, Vik1 or Cik1. A new crystal structure of the globular, C-terminal domain of Vik1 shows that the domain is structurally similar to the kinesin (and myosin) motor domain, but lacks a nucleotide-binding site. Strikingly, Vik1 binds to microtubules and could help regulate interactions of Kar3 with microtubules.
Allingham, J., Sproul. L., Rayment, I., & Gilbert, S. 2007. Vik1 modulates microtubule-Kar3 interactions through a motor domain that lacks an active site. Cell 128, 1161-1172.
Kinesin-1 in Live Cells
Studies on kinesin-1 in live cells using FRET between KHC and KLC show conformational changes that occur between an inactive folded state and active state. Activation not only requires separation of the KHC motor and tail domains, but involves a structural change that moves the motor domains closer together.
Cai, D., Hoppe, A. D., Swanson, J. A., & Verhey, K. J. 2007. Kinesin-1 structural organization and conformational changes revealed by FRET stoichiometry in live cells. J. Cell Biol. 176, 51-63.
Kinesin-13 Rings on Microtubules
The kinesin-13 motors depolymerize microtubules rather than move along the microtubule lattice like other kinesin motors. Analysis of kinesin-13-decorated microtubules by electron microscopy shows striking rings and spirals formed by the motor domain around the microtubules, reminiscent of the yeast Dam1 rings. Three-dimensional reconstructions and docking of motor and tubulin crystal structures indicate that the rings consist of a tubulin protofilament that spirals around the microtubule, attached by dimeric motors that are bound to the microtubule. The kinesin-13 rings might help anchor the motor to the ends of microtubules during depolymerization.
Tan, D., Asenjo, A. B., Mennella, V., Sharp, D. J. & Sosa, H. 2006. Kinesin-13s form rings around microtubules. J. Cell Biol. 175, 25-31.
New Kinesin Motor Conformational Changes
Unusually high-resolution cryoelectron microscopy structures of the kinesin-14 motor, Kar3, bound to microtubules in three different nucleotide states show large, previously unreported structural changes between states. These include melting of the switch II helix alpha4, closure of the nucleotide-binding pocket, and distortion of the central beta sheet, reminiscent of changes in the beta sheet recently reported for myosin crystal structures. Distortion of the central beta sheet may represent the strain-producing conformational change of the kinesin motors that leads to force production.
Hirose, K., Akimaru, E., Akiba, T., Endow, S. A. & Amos, L. A. 2006. Large conformational changes in a kinesin motor catalyzed by interaction with microtubules. Molec. Cell 23, 913-923.
Kinesin-8 Microtubule Depolymerization
Analysis of the yeast kinesin-8 motor, Klp3p, shows that it is a microtubule depolymerase. The motor is unusual in that it depolymerizes microtubules only from the plus ends, rather than both ends like the kinesin-13s, and it depolymerizes long microtubules faster than short ones. Length-dependent depolymerization could be an important cellular mechanism for regulating the length of microtubule-based structures, e.g. the mitotic spindle.
Varga, V., Helenius, J., Tanaka, K., Hyman, A. A., Tanaka, T. U. & Howard, J. 2006. Yeast kinesin-8 depolymerizes microtubules in a length-dependent manner.Nat. Cell Biol.8, 957-962.
Return to the Kinesin Home Page.
Copyright 1996-2007. All rights reserved.
Created 20 November 1997 00:55 GMT
Modified 12 May 2007 6:40 GMT