ArticleProceedings of the National Academy of Sciences of the United States of America2014
Comprehensive structural model of the mechanochemical cycle of a mitotic motor highlights molecular adaptations in the kinesin family.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 64 citations in OpenAlex.
- Anisotropic unbinding and location-dependent hovering of a kinesin motor head over microtubule.Biophysical journal · 2026Article
- A Phosphorylation Switch Governs KIF11's Mechanical Output During Mitosis.bioRxiv : the preprint server for biology · 2026Article
- Selective regulation of kinesin-5 function by β-tubulin carboxy-terminal tails.The Journal of cell biology · 2025Article
- Noncanonical interaction with microtubules via the N-terminal nonmotor domain is critical for the functions of a bidirectional kinesin.Science advances · 2024Article
- Nucleotide-free structures of KIF20A illuminate atypical mechanochemistry in this kinesin-6.Open biology · 2023Article
- New insights into the mechanochemical coupling mechanism of kinesin-microtubule complexes from their high-resolution structures.Biochemical Society transactions · 2023Review
- A kinesin-1 variant reveals motor-induced microtubule damage in cells.Current biology : CB · 2022Article
- Downregulation of KIF15 inhibits the tumorigenesis of non-small-cell lung cancer via inactivating Raf/MEK/ERK signaling.Histology and histopathology · 2022Article
- KIF11 As a Potential Pan-Cancer Immunological Biomarker Encompassing the Disease Staging, Prognoses, Tumor Microenvironment, and Therapeutic Responses.Oxidative medicine and cellular longevity · 2022Article
- KIF5A upregulation in hepatocellular carcinoma: A novel prognostic biomarker associated with unique tumor microenvironment status.Frontiers in oncology · 2022Article
- Cryo-EM structure of a microtubule-bound parasite kinesin motor and implications for its mechanism and inhibition.The Journal of biological chemistry · 2021Article
- Article
- Mechanisms by Which Kinesin-5 Motors Perform Their Multiple Intracellular Functions.International journal of molecular sciences · 2021Review
- Pathogenic mutations in the kinesin-3 motor KIF1A diminish force generation and movement through allosteric mechanisms.The Journal of cell biology · 2021Article
- Bioinformatics Analysis of KIF1A Expression and Gene Regulation Network in Ovarian Carcinoma.International journal of general medicine · 2021Article
- The effects of osmolytes onRSC advances · 2020Article
- Article
- Structure of Microtubule-Trapped Human Kinesin-5 and Its Mechanism of Inhibition Revealed Using Cryoelectron Microscopy.Structure (London, England : 1993) · 2020Article
- Structural basis for power stroke vs. Brownian ratchet mechanisms of motor proteins.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- KIF5A Promotes Bladder Cancer ProliferationDisease markers · 2019Article
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Kinesins are responsible for a wide variety of microtubule-based, ATP-dependent functions. Their motor domain drives these activities, but the molecular adaptations that specify these diverse and essential cellular activities are poorly understood. It has been assumed that the first identified kinesin--the transport motor kinesin-1--is the mechanistic paradigm for the entire superfamily, but accumulating evidence suggests otherwise. To address the deficits in our understanding of the molecular basis of functional divergence within the kinesin superfamily, we studied kinesin-5s, which are essential mitotic motors whose inhibition blocks cell division. Using cryo-electron microscopy and determination of structure at subnanometer resolution, we have visualized conformations of microtubule-bound human kinesin-5 motor domain at successive steps in its ATPase cycle. After ATP hydrolysis, nucleotide-dependent conformational changes in the active site are allosterically propagated into rotations of the motor domain and uncurling of the drug-binding loop L5. In addition, the mechanical neck-linker element that is crucial for motor stepping undergoes discrete, ordered displacements. We also observed large reorientations of the motor N terminus that indicate its importance for kinesin-5 function through control of neck-linker conformation. A kinesin-5 mutant lacking this N terminus is enzymatically active, and ATP-dependent neck-linker movement and motility are defective, although not ablated. All these aspects of kinesin-5 mechanochemistry are distinct from kinesin-1. Our findings directly demonstrate the regulatory role of the kinesin-5 N terminus in collaboration with the motor's structured neck-linker and highlight the multiple adaptations within kinesin motor domains that tune their mechanochemistries according to distinct functional requirements.
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