9DHZ

Cryo-EM structure of HURP bound to a microtubule

Summary for 9DHZ

• Entry DOI: 10.2210/pdb9dhz/pdb
• EMDB information: 46893
• Descriptor: Disks large-associated protein 5, Tubulin beta chain, Tubulin alpha-1B chain, ... (7 entities in total)
• Functional Keywords: hurp, tubulin, k-fiber, mitosis, spindle, protein binding
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 5
• Total formula weight: 236937.42

Authors

Perez-Bertoldi, J.M.,Nogales, E. (deposition date: 2024-09-04, release date: 2025-07-16)

Primary citation

Perez-Bertoldi, J.M.,Zhao, Y.,Thawani, A.,Yildiz, A.,Nogales, E.
HURP regulates Kif18A recruitment and activity to synergistically control microtubule dynamics.
Nat Commun, 15:9687-9687, 2024

PubMed Abstract: 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. While sparse decoration of HURP activates the motor, higher concentrations hinder processive motility. To shed light on this behavior, we determine the binding mode of HURP to microtubules using cryo-EM. The structure helps rationalize why HURP functions as a microtubule stabilizer. Additionally, HURP partially overlaps with the microtubule-binding site of the Kif18A motor domain, indicating that excess HURP inhibits Kif18A motility by steric exclusion. We also observe that HURP and Kif18A function together to suppress dynamics of the microtubule plus-end, providing a mechanistic basis for how they collectively serve in microtubule length control.

PubMed: 39516196
DOI: 10.1038/s41467-024-53691-7

Experimental method

ELECTRON MICROSCOPY (3.1 Å)