Cited by 67Microtubule and mitosis dynamicsProtein Structure and Dynamicsstochastic dynamics and bifurcation

Electrostatically biased binding of kinesin to microtubules

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Grant, Barry J., M. Gheorghe, Dana, Zheng, Wenjun, Alonso, Maria, Huber, Gary, Dlugosz, Maciej, McCammon, J. Andrew, Cross, Robert A.·2011·PLoS Biology

Abstract

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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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
Published
2011-11-29
Volume
9
Issue
11
Pages
e1001207
ISSN
  • 1544-9173 (ISSN-L)
  • 1545-7885
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
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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