The mechanism and energetics of the dynein priming stroke.
| Autor: | Golcuk M; Department of Mechanical Engineering, Istanbul Technical University (ITU), Istanbul 34437, Turkey., Yilmaz SZ; Department of Mechanical Engineering, Istanbul Technical University (ITU), Istanbul 34437, Turkey., Yildiz A; Physics Department, University of California, Berkeley, Berkeley, CA 94720, USA; Department of Molecular and Cellular Biology, University of California, Berkeley, Berkeley, CA 94720, USA., Gur M; Department of Mechanical Engineering, Istanbul Technical University (ITU), Istanbul 34437, Turkey; Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, PA 15213, USA. Electronic address: gurme@itu.edu.tr. |
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| Jazyk: | angličtina |
| Zdroj: | Structure (London, England : 1993) [Structure] 2024 May 02; Vol. 32 (5), pp. 603-610.e4. Date of Electronic Publication: 2024 Mar 01. |
| DOI: | 10.1016/j.str.2024.02.003 |
| Abstrakt: | Dyneins are an AAA+ motor responsible for motility and force generation toward the minus end of microtubules. Dynein motility is powered by nucleotide-dependent transitions of its linker domain, which transitions between straight (post-powerstroke) and bent (pre-powerstroke) conformations. To understand the dynamics and energetics of the linker, we performed all-atom molecular dynamics simulations of human dynein-2 primed for its power stroke. Simulations revealed that the linker can adopt either a bent conformation or a semi-bent conformation, separated by a 5.7 kT energy barrier. The linker cannot switch back to its straight conformation in the pre-powerstroke state due to a steric clash with the AAA+ ring. Simulations also showed that an isolated linker has a free energy minimum near the semi-bent conformation in the absence of the AAA+ ring, indicating that the linker stores energy as it bends and releases this energy during the powerstroke. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2024 Elsevier Ltd. All rights reserved.) |
| Databáze: | MEDLINE |
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