The structure of the γ-TuRC: a 25-years-old molecular puzzle

Župa, Erik; Liu, Peng; Würtz, Martin; Schiebel, Elmar; Pfeffer, Stefan

doi:10.1016/j.sbi.2020.08.008

Cited by 29 publications

(19 citation statements)

References 48 publications

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“…At least eight different proteins assemble in defined stoichiometry to form the γ-TuRC [25]. In order to achieve expression of all subunits, we decided to subclone human γ-TuRC component genes into a modified MultiBac expression system [20].…”

Section: A Recombinant System For the Expression Of Gamma-ring Complex Proteins γ-Tubulin Actin And Mitotic Spindle Organizing Protein 1 mentioning

confidence: 99%

Reconstitution of the recombinant human γ-tubulin ring complex

et al. 2021

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Cryo-electron microscopy recently resolved the structure of the vertebrate γ-tubulin ring complex (γ-TuRC) purified from Xenopus laevis egg extract and human cells to near-atomic resolution. These studies clarified the arrangement and stoichiometry of γ-TuRC components and revealed that one molecule of actin and the small protein MZT1 are embedded into the complex. Based on this structural census of γ-TuRC core components, we developed a recombinant expression system for the reconstitution and purification of human γ-TuRC from insect cells. The recombinant γ-TuRC recapitulates the structure of purified native γ-TuRC and has similar functional properties in terms of microtubule nucleation and minus end capping. This recombinant system is a central step towards deciphering the activation mechanisms of the γ-TuRC and the function of individual γ-TuRC core components.

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Section: A Recombinant System For the Expression Of Gamma-ring Complex Proteins γ-Tubulin Actin And Mitotic Spindle Organizing Protein 1 mentioning

confidence: 99%

Reconstitution of the recombinant human γ-tubulin ring complex

et al. 2021

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“…Spokes 1–8 in γ-TuRC, containing four GCP(2–3) units, termed γ-tubulin small complexes (γ-TuSC), follow microtubule symmetry. On the other hand, spokes 9–14, containing GCP4–6, introduce asymmetry in both the diameter and pitch of γ-TuRC and are not compatible with microtubule symmetry [ 60 ]. This may explain why cytosolic γ-TuRC has low nucleation activity [ 55 ] and conformational changes in the γ-TuRC structure are necessary for its activation [ 61 ].…”

Section: γ-Tubulin and Microtubule Nucleation By γ-Tubulin Complexesmentioning

confidence: 99%

Dysregulation of Microtubule Nucleating Proteins in Cancer Cells

Dráberová

2021

Cancers

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In cells, microtubules typically nucleate from microtubule organizing centers, such as centrosomes. γ-Tubulin, which forms multiprotein complexes, is essential for nucleation. The γ-tubulin ring complex (γ-TuRC) is an efficient microtubule nucleator that requires additional centrosomal proteins for its activation and targeting. Evidence suggests that there is a dysfunction of centrosomal microtubule nucleation in cancer cells. Despite decades of molecular analysis of γ-TuRC and its interacting factors, the mechanisms of microtubule nucleation in normal and cancer cells remains obscure. Here, we review recent work on the high-resolution structure of γ-TuRC, which brings new insight into the mechanism of microtubule nucleation. We discuss the effects of γ-TuRC protein dysregulation on cancer cell behavior and new compounds targeting γ-tubulin. Drugs inhibiting γ-TuRC functions could represent an alternative to microtubule targeting agents in cancer chemotherapy.

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“…The centrosome of a related apicomplexan parasite Toxoplasma gondii, which does contain centrioles, shows a bipartite organization with a distinct inner and outer core (Suvorova et al, 2015). Furthermore, few canonical centrosome components are conserved in Plasmodium with the exception of centrins, a family of small calcium-binding proteins implicated in centrosome duplication (Azimzadeh & Bornens, 2007;Mahajan et al, 2008;Roques et al, 2019), and the microtubule nucleating complex around γ-tubulin (Zupa et al, 2020). Centrins have been used as bona fide centrosome marker and shown to localize distinctly for the nuclear DNA, possibly embedded in the nuclear envelope (Mahajan et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

An extended DNA-free intranuclear compartment organizes centrosome microtubules in malaria parasites

et al. 2021

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Proliferation of Plasmodium falciparum in red blood cells is the cause of malaria and is underpinned by an unconventional cell division mode, called schizogony. Contrary to model organisms, P. falciparum replicates by multiple rounds of nuclear divisions that are not interrupted by cytokinesis. Organization and dynamics of critical nuclear division factors remain poorly understood. Centriolar plaques, the centrosomes of P. falciparum, serve as microtubule organizing centers and have an acentriolar, amorphous structure. The small size of parasite nuclei has precluded detailed analysis of intranuclear microtubule organization by classical fluorescence microscopy. We apply recently developed super-resolution and time-lapse imaging protocols to describe microtubule reconfiguration during schizogony. Analysis of centrin, nuclear pore, and microtubule positioning reveals two distinct compartments of the centriolar plaque. Whereas centrin is extranuclear, we confirm by correlative light and electron tomography that microtubules are nucleated in a previously unknown and extended intranuclear compartment, which is devoid of chromatin but protein-dense. This study generates a working model for an unconventional centrosome and enables a better understanding about the diversity of eukaryotic cell division.

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The structure of the γ-TuRC: a 25-years-old molecular puzzle

Cited by 29 publications

References 48 publications

Reconstitution of the recombinant human γ-tubulin ring complex

Reconstitution of the recombinant human γ-tubulin ring complex

Dysregulation of Microtubule Nucleating Proteins in Cancer Cells

An extended DNA-free intranuclear compartment organizes centrosome microtubules in malaria parasites

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