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Loop L5 acts as a conformational latch in the Mitotic Kinesin Eg5

Behnke-Parks, W.M. and Vendome, J. and Honig, B. and Maliga, Z. and Moores, Carolyn A. and Rosenfeld, S.S. (2011) Loop L5 acts as a conformational latch in the Mitotic Kinesin Eg5. Journal of Biological Chemistry 286 (7), pp. 5242-5253. ISSN 0021-9258.

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Official URL: http://dx.doi.org/10.1074/jbc.M110.192930

Abstract

All members of the kinesin superfamily of molecular motors contain an unusual structural motif consisting of an alpha-helix that is interrupted by a flexible loop, referred to as L5. We have examined the function of L5 in the mitotic kinesin Eg5 by combining site-directed mutagenesis of L5 with transient state kinetics, molecular dynamics simulations, and docking using cryo electron microscopy density. We find that mutation of a proline residue located at a turn within this loop profoundly slows nucleotide-induced structural changes both at the catalytic site as well as at the microtubule binding domain and the neck linker. Molecular dynamics simulations reveal that this mutation affects the dynamics not only of L5 itself but also of the switch I structural elements that sense ATP binding to the catalytic site. Our results lead us to propose that L5 regulates the rate of conformational change in key elements of the nucleotide binding site through its interactions with alpha 3 and in so doing controls the speed of movement and force generation in kinesin motors.

Item Type: Article
Keyword(s) / Subject(s): Electron microscopy (EM), fluorescence, fluorescence resonance energy transfer (FRET), Kinesin, Kinetics, molecular dynamics, molecular motors
School or Research Centre: Birkbeck Schools and Research Centres > School of Science > Biological Sciences
Depositing User: Administrator
Date Deposited: 27 Jun 2011 13:11
Last Modified: 17 Apr 2013 12:20
URI: http://eprints.bbk.ac.uk/id/eprint/3568

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