de Jonge, Janeska J., Graw, Andreas, Kargas, Vasileios, Batters, Christopher, Montanarella, Antonino F., O’Loughlin, Tom, Johnson, Chloe, Arden, Susan D., Warren, Alan J., Geeves, Michael A., and others. (2024) Motor domain phosphorylation increases nucleotide exchange and turns MYO6 into a faster and stronger motor. Nature Communications, 15 (1). Article Number 6716. E-ISSN 2041-1723. (doi:10.1038/s41467-024-49898-3) (KAR id:106810)
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Official URL: https://doi.org/10.1038/s41467-024-49898-3 |
Abstract
Myosin motors perform many fundamental functions in eukaryotic cells by providing force generation, transport or tethering capacity. Motor activity control within the cell involves on/off switches, however, few examples are known of how myosins regulate speed or processivity and fine-tune their activity to a specific cellular task. Here, we describe a phosphorylation event for myosins of class VI (MYO6) in the motor domain, which accelerates its ATPase activity leading to a 4-fold increase in motor speed determined by actin-gliding assays, single molecule mechanics and stopped flow kinetics. We demonstrate that the serine/threonine kinase DYRK2 phosphorylates MYO6 at S267 in vitro. Single-molecule optical-tweezers studies at low load reveal that S267-phosphorylation results in faster nucleotide-exchange kinetics without change in the working stroke of the motor. The selective increase in stiffness of the acto-MYO6 complex when proceeding load-dependently into the nucleotide-free rigor state demonstrates that S267-phosphorylation turns MYO6 into a stronger motor. Finally, molecular dynamic simulations of the nucleotide-free motor reveal an alternative interaction network within insert-1 upon phosphorylation, suggesting a molecular mechanism, which regulates insert-1 positioning, turning the S267-phosphorylated MYO6 into a faster motor.
Item Type: | Article |
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DOI/Identification number: | 10.1038/s41467-024-49898-3 |
Additional information: | For the purpose of open access, the author has applied a CC BY public copyright licence to any Author Accepted Manuscript version arising from this submission. |
Subjects: | Q Science |
Divisions: | Divisions > Division of Natural Sciences > Biosciences |
Funders: |
Medical Research Council (https://ror.org/03x94j517)
Blood Cancer UK (https://ror.org/0055acf80) Rosetrees Trust (https://ror.org/04e3zg361) Wellcome Trust (https://ror.org/029chgv08) |
SWORD Depositor: | JISC Publications Router |
Depositing User: | JISC Publications Router |
Date Deposited: | 09 Aug 2024 10:34 UTC |
Last Modified: | 09 Aug 2024 16:30 UTC |
Resource URI: | https://kar.kent.ac.uk/id/eprint/106810 (The current URI for this page, for reference purposes) |
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