Directionality of dynein is controlled by the angle and length of its stalk
Abstract
The ability of cytoskeletal motors to move unidirectionally along filamentous tracks is central to their role in cargo transport, motility and cell division. Kinesin and myosin motor families have a subclass that moves towards the opposite end of the microtubule or actin filament with respect to the rest of the motor family, whereas all dynein motors that have been studied so far exclusively move towards the minus end of the microtubule. Guided by cryo-electron microscopy and molecular dynamics simulations, we sought to understand the mechanism that underpins the directionality of dynein by engineering a Saccharomyces cerevisiae dynein that is directed towards the plus end of the microtubule. Here, using single-molecule assays, we show that elongation or shortening of the coiled-coil stalk that connects the motor to the microtubule controls the helical directionality of dynein around microtubules. By changing the length and angle of the stalk, we successfully reversed the motility towards the plus end of the microtubule. These modifications act by altering the direction in which the dynein linker swings relative to the microtubule, rather than by reversing the asymmetric unbinding of the motor from the microtubule. Lastly, because the length and angle of the dynein stalk are fully conserved amongmore »
- Authors:
-
- Univ. of California, Berkeley, CA (United States). Dept. of Physics
- Medical Research Council, Lab. of Molecular Biology, Division of Structural Studies, Cambridge (United Kingdom)
- Istanbul Technical Univ., Istanbul, Turkey). Dept. of Mechanical Engineering
- Univ. of California, Berkeley, CA (United States). Dept. of Physics; Univ. of California, Berkeley, CA (United States). Dept. of Molecular and Cellular Biology
- Publication Date:
- Research Org.:
- Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC)
- OSTI Identifier:
- 1571970
- Grant/Contract Number:
- AC02-05CH11231
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Nature (London)
- Additional Journal Information:
- Journal Name: Nature (London); Journal Volume: 566; Journal Issue: 7744; Journal ID: ISSN 0028-0836
- Publisher:
- Nature Publishing Group
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES
Citation Formats
Can, Sinan, Lacey, Samuel, Gur, Mert, Carter, Andrew P., and Yildiz, Ahmet. Directionality of dynein is controlled by the angle and length of its stalk. United States: N. p., 2019.
Web. doi:10.1038/s41586-019-0914-z.
Can, Sinan, Lacey, Samuel, Gur, Mert, Carter, Andrew P., & Yildiz, Ahmet. Directionality of dynein is controlled by the angle and length of its stalk. United States. https://doi.org/10.1038/s41586-019-0914-z
Can, Sinan, Lacey, Samuel, Gur, Mert, Carter, Andrew P., and Yildiz, Ahmet. Wed .
"Directionality of dynein is controlled by the angle and length of its stalk". United States. https://doi.org/10.1038/s41586-019-0914-z. https://www.osti.gov/servlets/purl/1571970.
@article{osti_1571970,
title = {Directionality of dynein is controlled by the angle and length of its stalk},
author = {Can, Sinan and Lacey, Samuel and Gur, Mert and Carter, Andrew P. and Yildiz, Ahmet},
abstractNote = {The ability of cytoskeletal motors to move unidirectionally along filamentous tracks is central to their role in cargo transport, motility and cell division. Kinesin and myosin motor families have a subclass that moves towards the opposite end of the microtubule or actin filament with respect to the rest of the motor family, whereas all dynein motors that have been studied so far exclusively move towards the minus end of the microtubule. Guided by cryo-electron microscopy and molecular dynamics simulations, we sought to understand the mechanism that underpins the directionality of dynein by engineering a Saccharomyces cerevisiae dynein that is directed towards the plus end of the microtubule. Here, using single-molecule assays, we show that elongation or shortening of the coiled-coil stalk that connects the motor to the microtubule controls the helical directionality of dynein around microtubules. By changing the length and angle of the stalk, we successfully reversed the motility towards the plus end of the microtubule. These modifications act by altering the direction in which the dynein linker swings relative to the microtubule, rather than by reversing the asymmetric unbinding of the motor from the microtubule. Lastly, because the length and angle of the dynein stalk are fully conserved among species, our findings provide an explanation for why all dyneins move towards the minus end of the microtubule.},
doi = {10.1038/s41586-019-0914-z},
journal = {Nature (London)},
number = 7744,
volume = 566,
place = {United States},
year = {Wed Feb 06 00:00:00 EST 2019},
month = {Wed Feb 06 00:00:00 EST 2019}
}
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Works referencing / citing this record:
Pac1/LIS1 stabilizes an uninhibited conformation of dynein to coordinate its localization and activity
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