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    Conserved mechanisms of microtubule-stimulated ADP release, ATP binding, and force generation in transport kinesins

    Atherton, Joseph and Farabella, Irene and Yu, I-M. and Rosenfeld, S.S. and Houdusse, A. and Topf, Maya and Moores, Carolyn A. (2014) Conserved mechanisms of microtubule-stimulated ADP release, ATP binding, and force generation in transport kinesins. eLife 3 , ISSN 2050-084X.

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    Abstract

    Kinesins are a superfamily of microtubule-based ATP-powered motors, important for multiple, essential cellular functions. How microtubule binding stimulates their ATPase and controls force generation is not understood. To address this fundamental question, we visualized microtubule-bound kinesin-1 and kinesin-3 motor domains at multiple steps in their ATPase cycles - including their nucleotide-free states - at ~7Å resolution using cryo-electron microscopy. In both motors, microtubule binding promotes ordered conformations of conserved loops that stimulate ADP release, enhance microtubule affinity and prime the catalytic site for ATP binding. ATP binding causes only small shifts of these nucleotide-coordinating loops but induces large conformational changes elsewhere that allow force generation and neck linker docking towards the microtubule plus end. Family-specific differences across the kinesin-microtubule interface account for the distinctive properties of each motor. Our data thus provide evidence for a conserved ATP-driven mechanism for kinesins and reveal the critical mechanistic contribution of the microtubule interface.

    Metadata

    Item Type: Article
    School: Birkbeck Schools and Departments > School of Science > Biological Sciences
    Research Centre: Bioinformatics, Bloomsbury Centre for, Structural Molecular Biology, Institute of (ISMB)
    Depositing User: Administrator
    Date Deposited: 15 Sep 2014 09:11
    Last Modified: 07 Dec 2016 15:02
    URI: http://eprints.bbk.ac.uk/id/eprint/10519

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