9I8M

NEDD1-bound native vertebrate gamma-tubulin ring complex from Xenopus laevis, focused reconstruction

Summary for 9I8M

• Entry DOI: 10.2210/pdb9i8m/pdb
• EMDB information: 52729
• Descriptor: Gamma-tubulin complex component, Gamma-tubulin complex component 3 homolog, Gamma-tubulin complex component 6, ... (7 entities in total)
• Functional Keywords: cytoskeleton, microtubule, microtubule nucleation, complex, template, cap, gamma-tubulin, gamma-tubulin ring complex, cell cycle, nedd1, neural precursor cell-expressed developmentally down-regulated 1
• Biological source: Xenopus laevis (African clawed frog); More
• Total number of polymer chains: 27
• Total formula weight: 2150230.17

Authors

Vermeulen, B.J.A.,Pfeffer, S. (deposition date: 2025-02-05, release date: 2025-03-19, Last modification date: 2025-03-26)

Primary citation

Gao, Q.,Hofer, F.W.,Filbeck, S.,Vermeulen, B.J.A.,Wurtz, M.,Neuner, A.,Kaplan, C.,Zezlina, M.,Sala, C.,Shin, H.,Gruss, O.J.,Schiebel, E.,Pfeffer, S.
Structural mechanisms for centrosomal recruitment and organization of the microtubule nucleator gamma-TuRC.
Nat Commun, 16:2453-2453, 2025

PubMed Abstract: The γ-tubulin ring complex (γ-TuRC) acts as a structural template for microtubule formation at centrosomes, associating with two main compartments: the pericentriolar material and the centriole lumen. In the pericentriolar material, the γ-TuRC is involved in microtubule organization, while the function of the centriole lumenal pool remains unclear. The conformational landscape of the γ-TuRC, which is crucial for its activity, and its centrosomal anchoring mechanisms, which determine γ-TuRC activity and turnover, are not understood. Using cryo-electron tomography, we analyze γ-TuRCs in human cells and purified centrosomes. Pericentriolar γ-TuRCs simultaneously associate with the essential adapter NEDD1 and the microcephaly protein CDK5RAP2. NEDD1 forms a tetrameric structure at the γ-TuRC base through interactions with four GCP3/MZT1 modules and GCP5/6-specific extensions, while multiple copies of CDK5RAP2 engage the γ-TuRC in two distinct binding patterns to promote γ-TuRC closure and activation. In the centriole lumen, the microtubule branching factor Augmin tethers a condensed cluster of γ-TuRCs to the centriole wall with defined directional orientation. Centriole-lumenal γ-TuRC-Augmin is protected from degradation during interphase and released in mitosis to aid chromosome alignment. This study provides a unique view on γ-TuRC structure and molecular organization at centrosomes and identifies an important cellular function of centriole-lumenal γ-TuRCs.

PubMed: 40074789
DOI: 10.1038/s41467-025-57729-2

Experimental method

ELECTRON MICROSCOPY (4.3 Å)