Modular assembly of the principal microtubule nucleator γ-TuRC

Autor: Würtz, Martin, Zupa, Erik, Atorino, Enrico S., Neuner, Annett, Böhler, Anna, Rahadian, Ariani S., Vermeulen, Bram J. A., Tonon, Giulia, Eustermann, Sebastian, Schiebel, Elmar, Pfeffer, Stefan
Rok vydání: 2022
Předmět:
Zdroj: Nature Communications
Nature Communications, Vol 13, Iss 1, Pp 1-16 (2022)
ISSN: 2041-1723
DOI: 10.1038/s41467-022-28079-0
Popis: The gamma-tubulin ring complex (γ-TuRC) is the principal microtubule nucleation template in vertebrates. Recent cryo-EM reconstructions visualized the intricate quaternary structure of the γ-TuRC, containing more than thirty subunits, raising fundamental questions about γ-TuRC assembly and the role of actin as an integral part of the complex. Here, we reveal the structural mechanism underlying modular γ-TuRC assembly and identify a functional role of actin in microtubule nucleation. During γ-TuRC assembly, a GCP6-stabilized core comprising GCP2-3-4-5-4-6 is expanded by stepwise recruitment, selective stabilization and conformational locking of four pre-formed GCP2-GCP3 units. Formation of the lumenal bridge specifies incorporation of the terminal GCP2-GCP3 unit and thereby leads to closure of the γ-TuRC ring in a left-handed spiral configuration. Actin incorporation into the complex is not relevant for γ-TuRC assembly and structural integrity, but determines γ-TuRC geometry and is required for efficient microtubule nucleation and mitotic chromosome alignment in vivo.
The human microtubule nucleator γ-TuRC is composed of more than thirty subunits, including actin. Here the authors reveal the structural mechanism of modular γ-TuRC assembly and show a functional role of actin in microtubule nucleation.
Databáze: OpenAIRE
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