9h9p
From Proteopedia
Spokes 12 and 13 of the human gamma-tubulin ring complex in complex with CDK5RAP2 and docked MZT2/GCP2-NHD module
Structural highlights
DiseaseCK5P2_HUMAN Autosomal recessive primary microcephaly. The disease is caused by variants affecting the gene represented in this entry. FunctionCK5P2_HUMAN Potential regulator of CDK5 activity via its interaction with CDK5R1. Negative regulator of centriole disengagement (licensing) which maintains centriole engagement and cohesion. Involved in regulation of mitotic spindle orientation (By similarity). Plays a role in the spindle checkpoint activation by acting as a transcriptional regulator of both BUBR1 and MAD2 promoter. Together with EB1/MAPRE1, may promote microtubule polymerization, bundle formation, growth and dynamics at the plus ends. Regulates centrosomal maturation by recruitment of the gamma-tubulin ring complex (gamma-TuRC) onto centrosomes (PubMed:26485573). In complex with PDE4DIP isoform 13/MMG8/SMYLE, MAPRE1 and AKAP9, contributes to microtubules nucleation and extension from the centrosome to the cell periphery (PubMed:29162697). Required for the recruitment of AKAP9 to centrosomes (PubMed:29162697). Plays a role in neurogenesis (By similarity).[UniProtKB:Q8K389][1] [2] [3] [4] [5] [6] Publication Abstract from PubMedThe gamma-tubulin ring complex (gamma-TuRC) is a structural template for controlled nucleation of microtubules from alpha/beta-tubulin heterodimers. At the cytoplasmic side of the yeast spindle pole body, the CM1-containing receptor protein Spc72 promotes gamma-TuRC assembly from seven gamma-tubulin small complexes (gamma-TuSCs) and recruits the microtubule polymerase Stu2, yet their molecular interplay remains unclear. Here, we determine the cryo-EM structure of the Candida albicans cytoplasmic nucleation unit at 3.6 A resolution, revealing how the gamma-TuRC is assembled and conformationally primed for microtubule nucleation by the dimerised Spc72 CM1 motif. Two coiled-coil regions of Spc72 interact with the conserved C-terminal alpha-helix of Stu2 and thereby position the alpha/beta-tubulin-binding TOG domains of Stu2 in the vicinity of the microtubule assembly site. Collectively, we reveal the function of CM1 motifs in gamma-TuSC oligomerisation and the recruitment of microtubule polymerases to the gamma-TuRC. Structural insights into the interplay between microtubule polymerases, gamma-tubulin complexes and their receptors.,Zheng A, Vermeulen BJA, Wurtz M, Neuner A, Lubbehusen N, Mayer MP, Schiebel E, Pfeffer S Nat Commun. 2025 Jan 5;16(1):402. doi: 10.1038/s41467-024-55778-7. PMID:39757296[7] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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