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Distinguishing Inchworm and Hand-Over-Hand Processive Kinesin Movement by Neck Rotation Measurements
Abstract
The motor enzyme kinesin makes hundreds of unidirectional 8-nanometer steps without detaching from or freely sliding along the microtubule on which it moves. We investigated the kinesin stepping mechanism by immobilizing a Drosophila kinesin derivative through the carboxyl-terminal end of the neck coiled-coil domain and measuring orientations of microtubules moved by single enzyme molecules at submicromolar adenosine triphosphate concentrations. The kinesin-mediated microtubule-surface linkage was sufficiently torsionally stiff (>/=2.0 +/- 0.9 x 10(-20) Newton meters per radian2) that stepping by the hypothesized symmetric hand-over-hand mechanism would produce 180 degree rotations of the microtubule relative to the immobilized kinesin neck. In fact, there were no rotations, a finding that is inconsistent with symmetric hand-over-hand movement. An alternative "inchworm" mechanism is consistent with our experimental results.
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“In this model, the leading motor is always leading, the trailing motor is always trailing, and one motor remains enzymatically inactive throughout a processive run.”
From Stepping and Stretching (2003) · cites this paper as [33]
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“…the first one is “hand-over-hand” mechanism, where the kinesin heads step past one another, alternating the lead position (Yildiz et al. 2004), and the second is “inchworm” mechanism, where one kinesin head always leads, moving forward a step before the trailing head catches up (Hua et al. 2002).”
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“Hua et al. (2002) sought for, but did not observe, the 180° reorientations that would accompany every step in kinesin.”
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“Conventional kinesin-1 walks along microtubule toward the plus end in an asymmetric hand-over-hand manner [5,6,7,8].”
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“While that study is given a parenthetical reference, Hua et al. ignored its substance. As I said, the “inchworm episode” took place entirely within the context of an experimental program dedicated to characterizing, rather than explaining, the phenomenon of kinesin motility.17 So, what led these researchers to reject…”
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“The microscopic mechanical motions of the motor, however, are still obscure and hand-over-hand models (Peskin and Oster, 1995) are debated against inchworm models (Derényi and Vicsek, 1996; Hua et al., 2002).”
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“The inchworm model [21] proposed that only one head catalyzes ATP and always leads while the other head follows.”
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“We highlight that this is a consequence of the homodimer symmetry and does not necessarily hold for heterodimeric motors [64], or for motors deviating from the hand-over-hand stepping mechanism (e.g., using an inchworm mechanism [65, 66]).”
Single‐molecule tethered particle motion to study protein‐DNA interaction
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The Orphan Kinesin PAKRP2 Achieves Processive Motility Via Noncanonical Stepping
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“Inchworm-like stepping in this case differs from the originally 366 proposed inchworm model in that it involves two catalytically active motor domains (66, 67), and 367 therefore two ATP molecules are burned per 8.”
BackgroundCytoskeleton: The worm that never turns
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Metadata
- Authors
- Hua, W., Chung, J., & Gelles, J.
- Affiliations
- Biophysics and Structural Biology Program,
- Brandeis University (US)
- Corresponding author
- Gelles, Jeff
- Venue
- Science
- Published
- 2002-02
- Volume
- 295
- Issue
- 5556
- Pages
- 844-848
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W1589896765
- Cited by
- 194
- References
- 0
- Citations by year
- 2025: 3 · 2024: 3 · 2023: 3 · 2022: 3 · 2021: 3 · 2020: 4 · 2019: 4 · 2018: 5 · 2017: 4 · 2016: 7 · 2015: 3 · 2014: 10 · 2013: 4 · 2012: 14
- FWCI
- 7.66
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Physical Sciences › Physics and Astronomy › Atomic and Molecular Physics, and Optics › Force Microscopy Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Keywords
- kinesin, inchworm mechanism, hand-over-hand mechanism, torsional stiffness, microtubule sliding
- MeSH terms
- Adenosine Triphosphate, Adenylyl Imidodiphosphate, Animals, Binding Sites, Catalysis, Drosophila, Enzymes, Immobilized, Microtubules, Models, Biological, Movement, Rotation, Kinesins, Protein Structure, Tertiary, Dimerization, Streptavidin, Molecular Motor Proteins
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