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Kinesin-8 motors regulate kinetochore-microtubule dynamics and control spindle length and positioning. Certain isoforms achieve this by traversing microtubules, accumulating at plus-ends, and depolymerizing terminal αβ-tubulin subunits. While the kinesin-8 motor domain is well characterized, the tail domain regions are less understood. Using the Candida albicans Kip3 protein as a model for fungal kinesin-8, we present an X-ray crystal structure and hydrodynamic analysis of its motor-proximal tail segment, revealing its role in motor dimerization. This segment forms a compact, 92 Å-long four-helix bundle, rather than an elongated coiled-coil stalk seen in most kinesins. The bundle is stabilized primarily by interactions between helices one and three, with additional support from helices two and four. A flexible hinge bisects the bundle into two lobules, imparting mechanical pliability and asymmetric exterior surfaces. These unique features may facilitate interactions with regulatory elements or contribute to the functional versatility of kinesin-8 motors.
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http://dx.doi.org/10.1016/j.str.2025.08.011 | DOI Listing |
J Cell Biol
October 2025
Department of Cell and Developmental Biology, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Carboxy-terminal tails (CTTs) of tubulin proteins are sites of regulating microtubule function. We previously conducted a genetic interaction screen and identified Kip3, a kinesin-8 motor, as potentially requiring the β-tubulin CTT (β-CTT) for function. Here we use budding yeast to define how β-CTT promotes Kip3 function and the features of β-CTT that are important for this mechanism.
View Article and Find Full Text PDFStructure
September 2025
Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON K7L 3N6, Canada. Electronic address:
Kinesin-8 motors regulate kinetochore-microtubule dynamics and control spindle length and positioning. Certain isoforms achieve this by traversing microtubules, accumulating at plus-ends, and depolymerizing terminal αβ-tubulin subunits. While the kinesin-8 motor domain is well characterized, the tail domain regions are less understood.
View Article and Find Full Text PDFImmunotargets Ther
February 2025
Department of General Practice, Honghui Hospital, Xi'an Jiaotong University, Xi'an, Shaanxi, 710054, People's Republic of China.
Purpose: Kinesin family member 18A (KIF18A) is a member of the kinesin-8 family of motor proteins, involved in the progression and metastasis of various tumors. However, its role in pancreatic adenocarcinoma (PAAD) remains unclear.
Methods: To evaluate that role, RNA sequencing datasets, complemented by pertinent clinical metadata, were procured from the Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) repositories.
Proc Natl Acad Sci U S A
November 2024
Laboratory of Cell Biophysics, Division of Molecular Biology, Ruđer Bošković Institute, Zagreb 10000, Croatia.
Cancer cells often display errors in chromosome segregation, some of which result from improper chromosome alignment at the spindle midplane. Chromosome alignment is facilitated by different rates of microtubule poleward flux between sister kinetochore fibers. However, the role of the poleward flux in supporting mitotic fidelity remains unknown.
View Article and Find Full Text PDFNat Commun
November 2024
Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA.
During mitosis, microtubule dynamics are regulated to ensure proper alignment and segregation of chromosomes. The dynamics of kinetochore-attached microtubules are regulated by hepatoma-upregulated protein (HURP) and the mitotic kinesin-8 Kif18A, but the underlying mechanism remains elusive. Using single-molecule imaging in vitro, we demonstrate that Kif18A motility is regulated by HURP.
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