6tf9
Structure of the vertebrate gamma-Tubulin Ring Complex
Structural highlights
FunctionPublication Abstract from PubMedMicrotubules (MTs) are dynamic polymers of alphabeta-tubulin and play critical roles in cell signaling, cell migration, intracellular transport processes and chromosome segregation(1). They assemble de novo from alpha/beta-tubulin dimers in an essential process termed MT nucleation. Complexes containing the protein gamma-tubulin serve as structural templates for the MT nucleation reaction(2). In vertebrates, MTs are nucleated by the 2.2 MDa gamma-tubulin ring complex (gamma-TuRC) composed of gamma-tubulin, five related gamma-tubulin complex proteins (GCP2-6) and additional factors(3). GCP6 is unique among the GCP proteins, because it carries an extended insertion domain of unknown function. High-resolution structural information on the gamma-TuRC is not available, strongly limiting our understanding of MT formation in cells and tissue(2). Here, we present the cryo-EM structure of gamma-TuRC from Xenopus laevis at 4.8 A global resolution, revealing a 14-spoked arrangement of GCPs and gamma-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 gamma-TuRC. Unexpectedly, we identified Actin as a bona fide structural component of gamma-TuRC with functional relevance in MT nucleation. The gamma-TuRC spiral geometry is suboptimal for MT nucleation and a controlled conformational rearrangement of the gamma-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 gamma-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 biogensis(4). Insights into the assembly and activation of the microtubule nucleator gamma-TuRC.,Liu P, Zupa E, Neuner A, Bohler A, Loerke J, Flemming D, Ruppert T, Rudack T, Peter C, Spahn C, Gruss OJ, Pfeffer S, Schiebel E Nature. 2019 Dec 19. pii: 10.1038/s41586-019-1896-6. doi:, 10.1038/s41586-019-1896-6. PMID:31856152[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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