Key residues on microtubule responsible for activation of kinesin ATPase

Seiichi Uchimura*, Yusuke Oguchi, You Hachikubo, Shin'Ichi Ishiwata, Etsuko Muto

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    43 Citations (Scopus)


    Microtubule (MT) binding accelerates the rate of ATP hydrolysis in kinesin. To understand the underlying mechanism, using charged-to-alanine mutational analysis, we identified two independent sites in tubulin, which are critical for kinesin motility, namely, a cluster of negatively charged residues spanning the helix 11-12 (H11-12) loop and H12 of α-tubulin, and the negatively charged residues in H12 of Β-tubulin. Mutation in the α-tubulin- binding site results in a deceleration of ATP hydrolysis (k cat), whereas mutation in the Β-tubulin-binding site lowers the affinity for MTs (K 0.5 MT). The residue E415 in α-tubulin seems to be important for coupling MT binding and ATPase activation, because the mutation at this site results in a drastic reduction in the overall rate of ATP hydrolysis, largely due to a deceleration in the reaction of ADP release. Our results suggest that kinesin binding at a region containing α-E415 could transmit a signal to the kinesin nucleotide pocket, triggering its conformational change and leading to the release of ADP.

    Original languageEnglish
    Pages (from-to)1167-1175
    Number of pages9
    JournalEMBO Journal
    Issue number7
    Publication statusPublished - 2010 Apr


    • ATPase kinetics
    • Kinesin
    • Microtubule
    • Motility
    • Mutant analysis

    ASJC Scopus subject areas

    • Molecular Biology
    • Biochemistry, Genetics and Molecular Biology(all)
    • Immunology and Microbiology(all)
    • Neuroscience(all)


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