Category Ranking

98%

Total Visits

921

Avg Visit Duration

2 minutes

Citations

20

Article Abstract

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.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.str.2025.08.011DOI Listing

Publication Analysis

Top Keywords

kinesin-8 motors
12
fungal kinesin-8
8
tail domain
8
motors dimerize
4
dimerize folding
4
folding proximal
4
proximal tail
4
domain compact
4
compact helical
4
bundle
4

Similar Publications

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 PDF

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 PDF

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.

View Article and Find Full Text PDF

Microtubule poleward flux as a target for modifying chromosome segregation errors.

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 PDF

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.

View Article and Find Full Text PDF