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  Quantification and demonstration of the collective constriction-by-ratchet mechanism in the dynamin molecular motor

Ganichkin, O. M., Vancraenenbroeck, R., Rosenblum, G., Hofmann, H., Mikhailov, A. S., Daumke, O., et al. (2021). Quantification and demonstration of the collective constriction-by-ratchet mechanism in the dynamin molecular motor. Proceedings of the National Academy of Sciences of the United States of America, 118(28): e2101144118. doi:10.1101/2020.09.10.289546.

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 Creators:
Ganichkin, Oleg M.1, Author
Vancraenenbroeck, Renee2, Author
Rosenblum, Gabriel3, Author
Hofmann, Hagen3, Author
Mikhailov, Alexander S.4, 5, Author              
Daumke, Oliver1, 6, Author
Noel, Jeffrey1, 4, Author              
Affiliations:
1Crystallography, Max Delbrück Center for Molecular Medicine, Berlin, Germany, ou_persistent22              
2Department of Structural and Molecular Biology, University College London, London, United Kingdom, ou_persistent22              
3Department of Structural Biology, Weizmann Institute of Science, Rehovot, Israel, ou_persistent22              
4Physical Chemistry, Fritz Haber Institute, Max Planck Society, ou_634546              
5Computational Molecular Biophysics, WPI Nano Life Science Institute, Kanazawa University, Kanazawa, Japan, ou_persistent22              
6Institute for Chemistry and Biochemistry, Free University of Berlin, Berlin, Germany, ou_persistent22              

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 Abstract: Dynamin oligomerizes into helical filaments on tubular membrane templates and, through constriction, cleaves them in a GTPase-driven way. Structural observations of GTP-dependent cross-bridges between neighboring filament turns have led to the suggestion that dynamin operates as a molecular ratchet motor. However, the proof of such mechanism remains absent. Particularly, it is not known whether a powerful enough stroke is produced and how the motor modules would cooperate in the constriction process. Here, we characterized the dynamin motor modules by single molecule (sm) FRET and found strong nucleotide-dependent conformational changes. Integrating smFRET with molecular dynamics simulations allowed us to determine the forces generated in a power stroke. Subsequently, the quantitative force data and the measured kinetics of the GT-Pase cycle were incorporated into a model including both a dynamin filament, with explicit motor cross-bridges, and a realistic deformable membrane template. In our simulations, collective constriction of the membrane by dynamin motor modules, based on the ratchet mechanism, is directly reproduced and analyzed. Functional parallels between the dynamin system and actomyosin in the muscle are seen. Through concerted action of the motors, tight membrane constriction to the hemifission radius can be reached. Our experimental and computational study provides an example of how collective motor action in megadalton molecular assemblies can be approached and explicitly resolved.

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Language(s): eng - English
 Dates: 2021-02-232021-05-242021-01-292021-07-13
 Publication Status: Published online
 Pages: 11
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Degree: -

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Title: Proceedings of the National Academy of Sciences of the United States of America
  Other : PNAS
  Abbreviation : Proc. Natl. Acad. Sci. U. S. A.
Source Genre: Journal
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Publ. Info: Washington, D.C. : National Academy of Sciences
Pages: 11 Volume / Issue: 118 (28) Sequence Number: e2101144118 Start / End Page: - Identifier: ISSN: 0027-8424
CoNE: https://pure.mpg.de/cone/journals/resource/954925427230