A nonmotor microtubule binding site in kinesin-5 is required for filament crosslinking and sliding
Open accessAbstract
Kinesin-5, a widely conserved motor protein required for assembly of the bipolar mitotic spindle in eukaryotes, forms homotetramers with two pairs of motor domains positioned at opposite ends of a dumbbell-shaped molecule [1-3]. It has long been assumed that this configuration of motor domains is the basis of kinesin-5's ability to drive relative sliding of microtubules [2, 4, 5]. Recently, it was suggested that in addition to the N-terminal motor domain, kinesin-5 also has a nonmotor microtubule binding site in its C terminus [6]. However, it is not known how the nonmotor domain contributes to motor activity, or how a kinesin-5 tetramer utilizes a combination of four motor and four nonmotor microtubule binding sites for its microtubule organizing functions. Here we show, in single molecule assays, that kinesin-5 homotetramers require the nonmotor C terminus for crosslinking and relative sliding of two microtubules. Remarkably, this domain enhances kinesin-5's microtubule binding without substantially reducing motor activity. Our results suggest that tetramerization of kinesin-5's low-processivity motor domains is not sufficient for microtubule sliding because the motor domains alone are unlikely to maintain persistent microtubule crosslinks. Rather, kinesin-5 utilizes nonmotor microtubule binding sites to tune its microtubule attachment dynamics, enabling it to efficiently align and sort microtubules during metaphase spindle assembly and function.
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Eg5 possesses another microtubule binding site in its tail that enhances motor processivity, microtubule association, and microtubule crosslinking.
“Furthermore, it was shown that Eg5 possesses another microtubule binding site in its tail that enhances motor processivity, microtubule association, and microtubule crosslinking [41], but it is still unknown how microtubule-binding events regulate the motor activity.”
From Regulatory mechanisms that control mitotic kinesins (2015) · cites this paper as [41]
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Regulatory mechanisms that control mitotic kinesins
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“It has been proposed that the tail-motor and/or tail-microtubule interaction triggers allosteric changes in the protein that mediate the switch of Eg5 motor activity between the two microtubule-binding states [41, 42].”
Background
- Authors
- Weinger, J. S., Qiu, M., Yang, G., & Kapoor, T. M.
- Affiliations
- Rockefeller University (US)
- Carnegie Mellon University (US)
- Corresponding author
- Kapoor, Tarun M.
- Venue
- Current Biology
- Publisher
- Elsevier BV
- Published
- 2011-01
- Volume
- 21
- Issue
- 2
- Pages
- 154-160
- ISSN
- 0960-9822 (ISSN-L)
- PMC
- PMC3049310
- OpenAlex
- W2043629514
- Cited by
- 100
- References
- 28
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 6 · 2023: 8 · 2022: 1 · 2021: 5 · 2020: 9 · 2019: 4 · 2018: 10 · 2017: 6 · 2016: 4 · 2015: 5 · 2014: 9 · 2013: 9 · 2012: 11
- FWCI
- 5.67
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Current Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Cancer Institute (T32CA 09673, T32CA009673)
- National Institute of General Medical Sciences (F32GM083566, GM065933, R01GM065933)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
- Health Sciences › Medicine › Oncology › Cancer Treatment and Pharmacology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Keywords
- kinesin-5, microtubule crosslinking, microtubule sliding, mitotic spindle assembly, C-terminal domain, single-molecule motility, metaphase spindle
- MeSH terms
- Animals, Binding Sites, Microtubules, Protein Binding, Kinesins, Xenopus Proteins
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