Directionality of dynein is controlled by the angle and length of its stalk

Can, Sinan; Lacey, Samuel; Gur, Mert; Carter, Andrew P.; Yildiz, Ahmet

doi:10.1038/s41586-019-0914-z

Directionality of dynein is controlled by the angle and length of its stalk

Journal Article · Tue Feb 05 23:00:00 EST 2019 · Nature (London)

DOI:https://doi.org/10.1038/s41586-019-0914-z· OSTI ID:1571970

Can, Sinan ^[1]; Lacey, Samuel ^[2]; Gur, Mert ^[3]; Carter, Andrew P. ^[2]; Yildiz, Ahmet ^[4]

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

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.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1571970

Journal Information:: Nature (London), Journal Name: Nature (London) Journal Issue: 7744 Vol. 566; ISSN 0028-0836

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

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Cargo adaptors regulate stepping and force generation of mammalian dynein–dynactin Elshenawy, Mohamed M.; Canty, John T.; Oster, Liya Nature Chemical Biology, Vol. 15, Issue 11 https://doi.org/10.1038/s41589-019-0352-0	journal	September 2019
Small stepping motion of processive dynein revealed by load-free high-speed single-particle tracking Ando, Jun; Shima, Tomohiro; Kanazawa, Riko Scientific Reports, Vol. 10, Issue 1 https://doi.org/10.1038/s41598-020-58070-y	journal	January 2020
Processivity of molecular motors under vectorial loads Khataee, Hamid; Mahamdeh, Mohammed; Neufeld, Zoltan Physical Review E, Vol. 102, Issue 2 https://doi.org/10.1103/physreve.102.022406	journal	August 2020
Structural basis for two-way communication between dynein and microtubules Nishida, Noritaka; Komori, Yuta; Takarada, Osamu Nature Communications, Vol. 11, Issue 1 https://doi.org/10.1038/s41467-020-14842-8	journal	February 2020
Pac1/LIS1 stabilizes an uninhibited conformation of dynein to coordinate its localization and activity Marzo, Matthew G.; Griswold, Jacqueline M.; Markus, Steven M. Nature Cell Biology, Vol. 22, Issue 5 https://doi.org/10.1038/s41556-020-0492-1	journal	April 2020
Lis1 activates dynein motility by modulating its pairing with dynactin Elshenawy, Mohamed M.; Kusakci, Emre; Volz, Sara Nature Cell Biology, Vol. 22, Issue 5 https://doi.org/10.1038/s41556-020-0501-4	journal	April 2020
Dynein harnesses active fluctuations of microtubules for faster movement Ezber, Yasin; Belyy, Vladislav; Can, Sinan Nature Physics, Vol. 16, Issue 3 https://doi.org/10.1038/s41567-019-0757-4	journal	January 2020
Coupling of ATPase activity, microtubule binding, and mechanics in the dynein motor domain Niekamp, Stefan; Coudray, Nicolas; Zhang, Nan The EMBO Journal, Vol. 38, Issue 13 https://doi.org/10.15252/embj.2018101414	journal	May 2019

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