9DUQ

HURP(65-174) bound to GMPCPP-stabilized microtubule

Summary for 9DUQ

• Entry DOI: 10.2210/pdb9duq/pdb
• EMDB information: 47173
• Descriptor: Disks large-associated protein 5, Tubulin beta chain, Tubulin alpha chain, ... (6 entities in total)
• Functional Keywords: microtubule, nucleation, spindle, oncogene, cell cycle
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 27
• Total formula weight: 932255.22

Authors

Ma, M.,Valdez, V.,Petry, S.,Zhang, R. (deposition date: 2024-10-03, release date: 2024-11-27)

Primary citation

Valdez, V.A.,Ma, M.,Gouveia, B.,Zhang, R.,Petry, S.
HURP facilitates spindle assembly by stabilizing microtubules and working synergistically with TPX2.
Nat Commun, 15:9689-9689, 2024

PubMed Abstract: In vertebrate spindles, most microtubules are formed via branching microtubule nucleation, whereby microtubules nucleate along the side of pre-existing microtubules. Hepatoma up-regulated protein (HURP) is a microtubule-associated protein that has been implicated in spindle assembly, but its mode of action is yet to be defined. In this study, we show that HURP is necessary for RanGTP-induced branching microtubule nucleation in Xenopus egg extract. Specifically, HURP stabilizes the microtubule lattice to promote microtubule formation from γ-TuRC. This function is shifted to promote branching microtubule nucleation through enhanced localization to TPX2 condensates, which form the core of the branch site on microtubules. Lastly, we provide a high-resolution cryo-EM structure of HURP on the microtubule, revealing how HURP binding stabilizes the microtubule lattice. We propose a model in which HURP stabilizes microtubules during their formation, and TPX2 preferentially enriches HURP to microtubules to promote branching microtubule nucleation and thus spindle assembly.

PubMed: 39516491
DOI: 10.1038/s41467-024-53630-6

Experimental method

ELECTRON MICROSCOPY (2.8 Å)