ATP turnover by individual myosin molecules hints at two conformers of the myosin active site
Open accessAbstract
Significance: Myosins use adenosine-5′-triphosphate (ATP) hydrolysis to drive motile functions, including muscle contraction. The main steps of ATP hydrolysis were previously identified by solution studies. Observing individual myosin molecules, one by one, interacting with fluorescently-labeled ATP, we found for one and the same myosin molecule two residence times for fluorescent ATP, a long lived, consistent with solution studies, and an unexpected short lived. Kinetic modeling suggests that this results from two active site conformers. In ensemble studies, generation of both dwell times from one myosin molecule had been indistinguishable from generation by a heterogeneous population of myosin molecules, demonstrating the power of molecule-by-molecule analysis to uncover previously undetected kinetic features and to distinguish, for example, different isoforms or mutant from wild-type molecules even in mixed populations.
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ATP turnover by individual myosin molecules uses two conformers of the active site: one allowing complete ATPase cycle, one dissociating ATP uncleaved.
“Recently, it has been found that ATP turnover by individual myosin molecules uses two conformers of the myosin active site, one that allows the complete ATPase cycle and one that dissociates ATP uncleaved.467”
From Protein Ensembles: How Does Nature Harness Thermodynamic Fluctuations for Life? The Diverse Functional Roles of Conformational Ensembles in the Cell (2016) · cites this paper as [467]
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- Authors
- Amrute-Nayak, M., Lambeck, K.-A., Radocaj, A., Huhnt, H. E., Scholz, T., Hahn, N., Tsiavaliaris, G., Walter, W. J., & Brenner, B.
- Affiliations
- Department of Molecular and Cell Physiology and
- Medizinische Hochschule Hannover (DE)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2014-02-03
- Volume
- 111
- Issue
- 7
- Pages
- 2536-2541
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3932867
- OpenAlex
- W2018967467
- Cited by
- 21
- References
- 37
- Citations by year
- 2025: 4 · 2024: 4 · 2023: 1 · 2022: 1 · 2021: 1 · 2020: 2 · 2019: 2 · 2017: 2 · 2016: 2 · 2015: 1 · 2014: 1
- FWCI
- 1.19
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Advanced Fluorescence Microscopy Techniques
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiomyopathy and Myosin Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- myosin, ATP turnover, chemo-mechanical coupling, ATPase kinetics, nucleotide binding, motor domain
- MeSH terms
- Adenosine Triphosphate, Computer Simulation, Hydrolysis, Kinetics, Microscopy, Fluorescence, Models, Chemical, Monte Carlo Method, Muscle Contraction, Myosins, Protein Conformation, Time Factors, Protein Isoforms
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