A universal pathway for kinesin stepping

Bason E. Clancy, William M. Behnke-Parks, Johan O.L. Andreasson, Steven S. Rosenfeld, Steven M. Block

Research output: Contribution to journalArticle

136 Scopus citations

Abstract

Kinesin-1 is an ATP-driven, processive motor that transports cargo along microtubules in a tightly regulated stepping cycle. Efficient gating mechanisms ensure that the sequence of kinetic events proceeds in the proper order, generating a large number of successive reaction cycles. To study gating, we created two mutant constructs with extended neck-linkers and measured their properties using single-molecule optical trapping and ensemble fluorescence techniques. Owing to a reduction in the inter-head tension, the constructs access an otherwise rarely populated conformational state in which both motor heads remain bound to the microtubule. ATP-dependent, processive backstepping and futile hydrolysis were observed under moderate hindering loads. On the basis of measurements, we formulated a comprehensive model for kinesin motion that incorporates reaction pathways for both forward and backward stepping. In addition to inter-head tension, we found that neck-linker orientation is also responsible for ensuring gating in kinesin.

Original languageEnglish (US)
Pages (from-to)1020-1027
Number of pages8
JournalNature Structural and Molecular Biology
Volume18
Issue number9
DOIs
StatePublished - Sep 2011

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

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    Clancy, B. E., Behnke-Parks, W. M., Andreasson, J. O. L., Rosenfeld, S. S., & Block, S. M. (2011). A universal pathway for kinesin stepping. Nature Structural and Molecular Biology, 18(9), 1020-1027. https://doi.org/10.1038/nsmb.2104