Insights into the assembly and activation of the microtubule nucleator γ-TuRC

• Verfasst von: Liu, Peng [VerfasserIn]
• Verfasst von: Župa, Erik [VerfasserIn]
• Verfasst von: Neuner, Annett [VerfasserIn]
• Verfasst von: Böhler, Anna [VerfasserIn]
• Verfasst von: Flemming, Dirk [VerfasserIn]
• Verfasst von: Ruppert, Thomas [VerfasserIn]
• Verfasst von: Pfeffer, Stefan [VerfasserIn]
• Verfasst von: Schiebel, Elmar [VerfasserIn]
• Titel: Insights into the assembly and activation of the microtubule nucleator γ-TuRC
• Verf.angabe: Peng Liu, Erik Zupa, Annett Neuner, Anna Böhler, Justus Loerke, Dirk Flemming, Thomas Ruppert, Till Rudack, Christoph Peter, Christian Spahn, Oliver J. Gruss, Stefan Pfeffer & Elmar Schiebel
• Jahr: 2020
• Jahr des Originals: 2019
• Umfang: 5 S.
• Fussnoten: Published online: 19 December 2019 ; Das PDF enthält zusätzlich einen Anhang von 26 Seiten ; Gesehen am 21.02.2020
• Titel Quelle: Enthalten in: Nature <London>
• Ort Quelle: London [u.a.] : Nature Publ. Group, 1869
• Jahr Quelle: 2020
• Band/Heft Quelle: 578(2020), Seite 467-471
• ISSN Quelle: 1476-4687
• DOI: doi:10.1038/s41586-019-1896-6
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1687635404

Abstract

Here, we present the cryo-EM structure of γ-TuRC from Xenopus laevis at 4.8 Å global resolution, revealing a 14-spoked arrangement of GCPs and γ-tubulins in a partially flexible open left-handed spiral with a uniform sequence of GCP variants (Fig. 1a). Via specific interactions with other GCP proteins, the GCP6-specific insertion domain scaffolds the assembly of the γ-TuRC. Unexpectedly, we identified Actin as a bona fide structural component of γ-TuRC with functional relevance in MT nucleation. The γ-TuRC spiral geometry is suboptimal for MT nucleation and a controlled conformational rearrangement of the γ-TuRC is required for its activation. Collectively, our cryo-EM reconstruction provides unprecedented insights into the molecular organization, the assembly and the activation mechanism of vertebrate γ-TuRC and will serve as an important framework for the mechanistic understanding of fundamental biological processes associated with MT nucleation, e.g. meiotic and mitotic spindle formation and centriole biogensis4.