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

Jawdat Al-Bassam, Yujia Cui, Dieter Klopfenstein, Bridget O. Carragher, Ronald D. Vale, Ronald A. Milligan

Research output: Contribution to journalArticle

55 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)743-753
Number of pages11
JournalJournal of Cell Biology
Volume163
Issue number4
DOIs
StatePublished - Nov 24 2003
Externally publishedYes

Keywords

  • C. elegans
  • Coiled coil
  • Cryo-EM
  • Dimerization
  • Microtubule

ASJC Scopus subject areas

  • Cell Biology

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    Al-Bassam, J., Cui, Y., Klopfenstein, D., Carragher, B. O., Vale, R. D., & Milligan, R. A. (2003). Distinct conformations of the kinesin Unc104 neck regulate a monomer to dimer motor transition. Journal of Cell Biology, 163(4), 743-753. https://doi.org/10.1083/jcb.200308020