Electrostatically biased binding of kinesin to microtubules
Open accessAbstract
The minimum motor domain of kinesin-1 is a single head. Recent evidence suggests that such minimal motor domains generate force by a biased binding mechanism, in which they preferentially select binding sites on the microtubule that lie ahead in the progress direction of the motor. A specific molecular mechanism for biased binding has, however, so far been lacking. Here we use atomistic Brownian dynamics simulations combined with experimental mutagenesis to show that incoming kinesin heads undergo electrostatically guided diffusion-to-capture by microtubules, and that this produces directionally biased binding. Kinesin-1 heads are initially rotated by the electrostatic field so that their tubulin-binding sites face inwards, and then steered towards a plus-endwards binding site. In tethered kinesin dimers, this bias is amplified. A 3-residue sequence (RAK) in kinesin helix alpha-6 is predicted to be important for electrostatic guidance. Real-world mutagenesis of this sequence powerfully influences kinesin-driven microtubule sliding, with one mutant producing a 5-fold acceleration over wild type. We conclude that electrostatic interactions play an important role in the kinesin stepping mechanism, by biasing the diffusional association of kinesin with microtubules.
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KIF1C E170A was able to protect the Golgi ribbon.
“KIF1C E170A, mutated in a conserved kinesin microtubule binding site (Woehlke et al., 1997; Grant et al., 2011), was also able to protect the Golgi ribbon.”
From The Rab6-regulated KIF1C kinesin motor domain contributes to Golgi organization (2015) · cites this paper as Grant et al., 2011
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- Authors
- Grant, B. J., M. Gheorghe, D., Zheng, W., Alonso, M., Huber, G., Dlugosz, M., McCammon, J. A., & Cross, R. A.
- Affiliations
- Howard Hughes Medical Institute (US)
- University at Buffalo, State University of New York (US)
- University of Warwick (GB)
- Corresponding author
- McCammon, J. Andrew
- Cross, Robert A.
- Venue
- PLoS Biology
- Publisher
- Public Library of Science (PLoS)
- Published
- 2011-11-29
- Volume
- 9
- Issue
- 11
- Pages
- e1001207
- ISSN
- 1544-9173 (ISSN-L)
- 1545-7885
- PMC
- PMC3226556
- OpenAlex
- W2035333393
- Cited by
- 67
- References
- 47
- Citations by year
- 2025: 2 · 2024: 3 · 2023: 4 · 2022: 6 · 2021: 4 · 2020: 2 · 2019: 7 · 2018: 2 · 2017: 5 · 2016: 5 · 2015: 5 · 2014: 8 · 2013: 10 · 2012: 4
- FWCI
- 3.37
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS Biology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Warwick Research Archive Portal (University of Warwick) (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Figshare (submittedVersion, cc-by)
- Funders
- National Science Foundation (0506593)
- Howard Hughes Medical Institute
- Marie Curie
- National Institutes of Health
- Center for Theoretical Biological Physics
- National Institute of General Medical Sciences (R01GM031749)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Physical Sciences › Physics and Astronomy › Statistical and Nonlinear Physics › stochastic dynamics and bifurcation
- Keywords
- kinesin-1, microtubule binding, electrostatic interactions, motor domain, microtubule sliding, Brownian dynamics, mutagenesis
- MeSH terms
- Binding Sites, Computer Simulation, Microtubules, Models, Molecular, Tubulin, Mutagenesis, Kinesins, Static Electricity
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