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TitleActivation and regulation of the dynein-dynactin-NuMA complex.
Journal, issue, pagesNat Chem Biol, Year 2026
Publish dateMar 16, 2026
AuthorsMerve Aslan / Ennio A d'Amico / Nathan H Cho / Aryan Taheri / Juan M Perez-Bertoldi / Yuanchang Zhao / Xinyue Zhong / Madeline Blaauw / Andrew P Carter / Sophie Dumont / Ahmet Yildiz /
PubMed AbstractDuring 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 ...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.
External linksNat Chem Biol / PubMed:41840068
MethodsEM (single particle)
Resolution6.53 - 6.78 Å
Structure data

EMDB-52171, PDB-9hhl:
Structure of Dynein-Dynactin-NuMA-LIS1
Method: EM (single particle) / Resolution: 6.53 Å

EMDB-52172: Dynactin pointed end in complex with NuMA
Method: EM (single particle) / Resolution: 6.78 Å

Chemicals

ChemComp-ADP:
ADENOSINE-5'-DIPHOSPHATE / ADP, energy-carrying molecule*YM

ChemComp-ATP:
ADENOSINE-5'-TRIPHOSPHATE / ATP, energy-carrying molecule*YM

ChemComp-ZN:
Unknown entry

Source
  • sus scrofa (pig)
  • homo sapiens (human)
KeywordsMOTOR PROTEIN / transport

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