Loop L5 acts as a conformational latch in the mitotic kinesin Eg5

William M. Behnke-Parks, Jeremie Vendome, Barry Honig, Zoltan Maliga, Carolyn Moores, Steven S. Rosenfeld

Research output: Contribution to journalArticlepeer-review

40 Scopus citations

Abstract

All members of the kinesin superfamily of molecular motors contain an unusual structural motif consisting of an α-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 α3 and in so doing controls the speed of movement and force generation in kinesin motors.

Original languageEnglish (US)
Pages (from-to)5242-5253
Number of pages12
JournalJournal of Biological Chemistry
Volume286
Issue number7
DOIs
StatePublished - Feb 18 2011

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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