Engineering controllable bidirectional molecular motors based on myosin
Open Access
- 19 February 2012
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature Nanotechnology
- Vol. 7 (4), 252-256
- https://doi.org/10.1038/nnano.2012.19
Abstract
Cytoskeletal motors drive the transport of organelles and molecular cargoes within cells1 and have potential applications in molecular detection and diagnostic devices2,3. Engineering molecular motors with controllable properties will allow selective perturbation of mechanical processes in living cells and provide optimized device components for tasks such as molecular sorting and directed assembly3. Biological motors have previously been modified by introducing activation/deactivation switches that respond to metal ions4,5 and other signals6. Here, we show that myosin motors can be engineered to reversibly change their direction of motion in response to a calcium signal. Building on previous protein engineering studies7,8,9,10,11 and guided by a structural model12 for the redirected power stroke of myosin VI, we have constructed bidirectional myosins through the rigid recombination of structural modules. The performance of the motors was confirmed using gliding filament assays and single fluorophore tracking. Our strategy, in which external signals trigger changes in the geometry and mechanics of myosin lever arms, should make it possible to achieve spatiotemporal control over a range of motor properties including processivity, stride size13 and branchpoint turning14.This publication has 34 references indexed in Scilit:
- Detailed Tuning of Structure and Intramolecular Communication Are Dispensable for Processive Motion of Myosin VIBiophysical Journal, 2011
- Structure of the torque ring of the flagellar motor and the molecular basis for rotational switchingNature, 2010
- Engineered Myosin VI Motors Reveal Minimal Structural Determinants of Directionality and ProcessivityJournal of Molecular Biology, 2009
- Spatiotemporal control of cell signalling using a light-switchable protein interactionNature, 2009
- Coarse-Grained Structural Modeling of Molecular Motors Using Multibody DynamicsCellular and Molecular Bioengineering, 2009
- The Mechanism of Ca2+-Dependent Regulation of Kinesin-Mediated Mitochondrial MotilityCell, 2009
- Calcium-Activated Myosin V Closes the Drosophila PupilCurrent Biology, 2008
- The Structural Basis for the Large Powerstroke of Myosin VICell, 2007
- The power stroke of myosin VI and the basis of reverse directionalityProceedings of the National Academy of Sciences of the United States of America, 2007
- The unique insert at the end of the myosin VI motor is the sole determinant of directionalityProceedings of the National Academy of Sciences of the United States of America, 2007