ArticleProceedings of the National Academy of Sciences of the United States of America2018
Structural consequences of hereditary spastic paraplegia disease-related mutations in kinesin.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 25 citations in OpenAlex.
- The Long Haul: Microtubule Motors as the Essential Supply Line for Neuronal Longevity.Journal of neurochemistry · 2026Review
- Auxin-inducible degradation of UNC-116 in C. elegans inhibits bidirectional dense core vesicle transport and worm locomotion on different timescales.Journal of cell science · 2026Article
- Kinesin superfamily proteins in ovarian cancer: from molecular mechanisms to clinical applications.Medical oncology (Northwood, London, England) · 2025Review
- One gene, many phenotypes: the role of KIF5A in neurodegenerative and neurodevelopmental diseases.Cell communication and signaling : CCS · 2025Review
- Altered molecular and cellular mechanisms in KIF5A-associated neurodegenerative or neurodevelopmental disorders.Cell death & disease · 2024Article
- The role of kinesin family members in hepatobiliary carcinomas: from bench to bedside.Biomarker research · 2024Review
- Article
- Road-blocker HSP disease mutation disrupts pre-organization for ATP hydrolysis in kinesin through a second sphere control.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Propofol attenuates kinesin-mediated axonal vesicle transport and fusion.Molecular biology of the cell · 2022Article
- Selective motor activation in organelle transport along axons.Nature reviews. Molecular cell biology · 2022Review
- Mechanistic basis of propofol-induced disruption of kinesin processivity.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Binding and transport of SFPQ-RNA granules by KIF5A/KLC1 motors promotes axon survival.The Journal of cell biology · 2021Article
- Anterograde Axonal Transport in Neuronal Homeostasis and Disease.Frontiers in molecular neuroscience · 2020Review
- Article
- Going Too Far Is the Same as Falling ShortFrontiers in cellular neuroscience · 2019Review
- Defects in Axonal Transport in Inherited Neuropathies.Journal of neuromuscular diseases · 2019Review
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A wide range of mutations in the kinesin motor Kif5A have been linked to a neuronal disorder called hereditary spastic paraplegia (HSP). The position of these mutations can vary, and a range of different motile behaviors have been observed, indicating that the HSP mutants can alter distinct aspects of kinesin mechanochemistry. While focusing on four key HSP-associated mutants, this study examined the structural and dynamic perturbations that arise from these mutations using a series of different computational methods, ranging from bioinformatics analyses to all-atom simulations, that account for solvent effects explicitly. We show that two catalytic domain mutations (R280S and K253N) reduce the microtubule (MT) binding affinity of the kinesin head domains appreciably, while N256S has a much smaller impact. Bioinformatics analysis suggests that the stalk mutation A361V perturbs motor dimerization. Subsequent integration of these effects into a coarse-grained structure-based model of dimeric kinesin revealed that the order-disorder transition of the neck linker is substantially affected, indicating a hampered directionality and processivity of kinesin. The present analyses therefore suggest that, in addition to kinesin-MT binding and coiled-coil dimerization, HSP mutations affecting motor stepping transitions and processivity can lead to disease.
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