9HHL

Structure of Dynein-Dynactin-NuMA-LIS1

This is a non-PDB format compatible entry.

Summary for 9HHL

• Entry DOI: 10.2210/pdb9hhl/pdb
• EMDB information: 52171
• Descriptor: Cytoplasmic dynein 1 intermediate chain 2, Dynactin 6, Dynactin subunit 5, ... (19 entities in total)
• Functional Keywords: motor protein, transport
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 41
• Total formula weight: 3953070.91

Authors

d'Amico, E.A.,Carter, A.P. (deposition date: 2024-11-21, release date: 2025-12-03, Last modification date: 2026-03-25)

Primary citation

Aslan, M.,d'Amico, E.A.,Cho, N.H.,Taheri, A.,Perez-Bertoldi, J.M.,Zhao, Y.,Zhong, X.,Blaauw, M.,Carter, A.P.,Dumont, S.,Yildiz, A.
Activation and regulation of the dynein-dynactin-NuMA complex.
Nat.Chem.Biol., 2026

PubMed Abstract: During cell division, the nuclear mitotic apparatus protein (NuMA) orchestrates the focusing of microtubule minus-ends in spindle poles and cortical force generation on astral microtubules by interacting with dynein motors, microtubules and other cellular factors. Here we used in vitro reconstitution, cryo-electron microscopy and live-cell imaging to understand the mechanism and regulation of NuMA. We determined the structure of the processive dynein-dynactin-NuMA complex (DDN) and showed that the NuMA N terminus drives dynein motility in vitro and facilitates dynein-mediated transport in live cells. The C terminus of NuMA directly binds and suppresses the dynamics of the microtubule minus-end. Full-length NuMA is autoinhibited for its interactions with dynein and microtubules, whereas mitotically phosphorylated NuMA activates dynein in vitro and interphase cells. Together with dynein, activated full-length NuMA focuses microtubule minus-ends into aster-like structures. These results provide critical insights into the activation of NuMA and dynein for their mitotic functions.

PubMed: 41840068
DOI: 10.1038/s41589-026-02156-7

Experimental method

ELECTRON MICROSCOPY (6.53 Å)