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Mechanism of Force Generation in Kinesin Motility

[+] Author Affiliations
Wonmuk Hwang

Texas A&M University, College Station, TX

Matthew J. Lang

Massachusetts Institute of Technology, Cambridge, MA

Paper No. SBC2007-175543, pp. 777-778; 2 pages
doi:10.1115/SBC2007-175543
From:
  • ASME 2007 Summer Bioengineering Conference
  • ASME 2007 Summer Bioengineering Conference
  • Keystone, Colorado, USA, June 20–24, 2007
  • Conference Sponsors: Bioengineering Division
  • ISBN: 0-7918-4798-5
  • Copyright © 2007 by ASME

abstract

Conventional kinesin is a dimeric motor protein that uses adenosine triphosphate (ATP) to walk processively along the microtubule. Although its nucleotide dependent conformational switching and binding of the neck linker (NL) on the motor head are known to be key events in kinesin motility, the basic mechanism by which it amplifies a small conformational change upon ATP binding to generate the force of the walking stroke has not been known. We combined structural analysis with a set of molecular dynamics simulations to identify the 9-residue long N-terminal region, which we named the ‘cover strand’ (CS), as an additional element essential for kinesin’s power stroke. It operates by differentially forming a β-sheet with NL when ATP binds, whereby the ‘cover-neck bundle’ (CNB) has an inherent conformational bias that drives NL into its binding pocket on the motor head. After the initial stroke, the later half of NL, starting with the ‘asparagine latch’ in the middle, forms specific bonds with the motor head to ensure tight binding. We constructed the force map generated by CNB, which showed a forward bias in agreement with single molecule motility measurements. Our result is consistent with other experimental observations, including the estimated stall force and the transverse anisotropy. The novel mechanism of force generation by the dynamic folding of CNB appears to hold in various kinesin families, and elucidates the economy in the design principle of the smallest known processive motor.

Copyright © 2007 by ASME

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