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Published 24 November 2003. doi:10.1083/jcb.200308020
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© The Rockefeller University Press, 0021-9525/2003/11/743 $8.00
The Journal of Cell Biology, Volume 163, Number 4, 743-753

Article

Distinct conformations of the kinesin Unc104 neck regulate a monomer to dimer motor transition



Jawdat Al-Bassam1,2, Yujia Cui3, Dieter Klopfenstein3, Bridget O. Carragher1,2, Ronald D. Vale3,4 and Ronald A. Milligan1,2

1 Department of Cell Biology, The Scripps Research Institute, La Jolla, CA 92037
2 Center for Integrative Molecular Biosciences, The Scripps Research Institute, La Jolla, CA 92037
3 Department of Molecular and Cellular Pharmacology, University of California, San Francisco, San Francisco, CA 94143
4 Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94143

Address correspondence to Ronald A. Milligan, Dept. of Cell Biology, CB-227, The Scripps Research Institute, 10550 North Torrey Pines Rd., La Jolla, CA 92037. Tel.: (858) 784-9827. Fax: (858) 784-2749. email: milligan{at}scripps.edu

Caenhorhabditis elegans Unc104 kinesin transports synaptic vesicles at rapid velocities. Unc104 is primarily monomeric in solution, but recent motility studies suggest that it may dimerize when concentrated on membranes. Using cryo-electron microscopy, we observe two conformations of microtubule-bound Unc104: a monomeric state in which the two neck helices form an intramolecular, parallel coiled coil; and a dimeric state in which the neck helices form an intermolecular coiled coil. The intramolecular folded conformation is abolished by deletion of a flexible hinge separating the neck helices, indicating that it acts as a spacer to accommodate the parallel coiled-coil configuration. The neck hinge deletion mutation does not alter motor velocity in vitro but produces a severe uncoordinated phenotype in transgenic C. elegans, suggesting that the folded conformation plays an important role in motor regulation. We suggest that the Unc104 neck regulates motility by switching from a self-folded, repressed state to a dimerized conformation that can support fast processive movement.

Key Words: coiled coil; dimerization; microtubule; cryo-EM; C. elegans

J. Al-Bassam and Y. Cui contributed equally to this work.

The online version of this paper contains supplemental material.

Abbreviations used in this paper: 3D, three-dimensional; AMPPNP, 5'-adenylylimidodiphosphate; FHA, forkhead homology associated; MRDD, mean radial density distribution; PH, pleckstrin homology.


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