Contribution of the myosin VI tail domain to processive stepping and intramolecular tension sensing
- 12 April 2010
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 107 (17), 7746-7750
- https://doi.org/10.1073/pnas.1002430107
Abstract
Myosin VI is proposed to act as both a molecular transporter and as an anchor in vivo. A portion of the molecule C-terminal to the canonical lever arm, termed the medial tail (MT), has been proposed to act as either a lever arm extension or as a dimerization motif. We describe constructs in which the MT is interrupted by a glycine-rich molecular swivel. Disruption of the MT results in decreased processive run lengths measured using single-molecule fluorescence microscopy and a decreased step size under applied load as measured in an optical trap. We used single-molecule gold nanoparticle tracking and optical trapping to examine the mechanism of coordination between the heads of dimeric myosin VI. We detect two rate-limiting kinetic processes at low (< 200 micromolar) ATP concentrations. Our data can be explained by a model in which intramolecular tension greatly increases the affinity of the lead head for ADP, likely by slowing ADP release from the lead head. This mechanism likely increases both the motor's processivity and its ability to act as an anchor under physiological conditions.Keywords
This publication has 52 references indexed in Scilit:
- Engineered Myosin VI Motors Reveal Minimal Structural Determinants of Directionality and ProcessivityJournal of Molecular Biology, 2009
- Myosin VI Dimerization Triggers an Unfolding of a Three-Helix Bundle in Order to Extend Its ReachMolecular Cell, 2009
- Direct observation of the mechanochemical coupling in myosin Va during processive movementNature, 2008
- Long single α-helical tail domains bridge the gap between structure and function of myosin VINature Structural & Molecular Biology, 2008
- Myosin VI Walks “Wiggly” on Actin with Large and Variable TiltingMolecular Cell, 2007
- How are the cellular functions of myosin VI regulated within the cell?Biochemical and Biophysical Research Communications, 2007
- How myosin VI coordinates its heads during processive movementThe EMBO Journal, 2007
- Myosin VI targeting to clathrin-coated structures and dimerization is mediated by binding to Disabled-2 and PtdIns(4,5)P2Nature, 2006
- Assembly dynamics of microtubules at molecular resolutionNature, 2006
- The mouse Snell's waltzer deafness gene encodes an unconventional myosin required for structural integrity of inner ear hair cellsNature Genetics, 1995