title: Crystal structure of γ-tubulin complex protein GCP4 provides insight into microtubule nucleation.
abstract: Microtubule nucleation in all eukaryotes involves γ-tubulin small complexes (γTuSCs) that comprise two molecules of γ-tubulin bound to γ-tubulin complex proteins (GCPs) GCP2 and GCP3. In many eukaryotes, multiple γTuSCs associate with GCP4, GCP5 and GCP6 into large γ-tubulin ring complexes (γTuRCs). Recent cryo-EM studies indicate that a scaffold similar to γTuRCs is formed by lateral association of γTuSCs, with the C-terminal regions of GCP2 and GCP3 binding γ-tubulin molecules. However, the exact role of GCPs in microtubule nucleation remains unknown. Here we report the crystal structure of human GCP4 and show that its C-terminal domain binds directly to γ-tubulin. The human GCP4 structure is the prototype for all GCPs, as it can be precisely positioned within the γTuSC envelope, revealing the nature of protein-protein interactions and conformational changes regulating nucleation activity.
authors: Institut de Pharmacologie et de Biologie Structurale, Centre National de la Recherche Scientifique, Toulouse, France.
authors: Valérie
authors: V
authors: Guillet
authors: Martine
authors: M
authors: Knibiehler
authors: Lynn
authors: L
authors: Gregory-Pauron
authors: Marie-Hélène
authors: MH
authors: Remy
authors: Cécile
authors: C
authors: Chemin
authors: Brigitte
authors: B
authors: Raynaud-Messina
authors: Cécile
authors: C
authors: Bon
authors: Justin M
authors: JM
authors: Kollman
authors: David A
authors: DA
authors: Agard
authors: Andreas
authors: A
authors: Merdes
authors: Lionel
authors: L
authors: Mourey
mesh_terms: D001665:Binding Sites; D018360:Crystallography, X-Ray; D006801:Humans; D008869:Microtubule-Associated Proteins / Q000737:chemistry* / Q000502:physiology; D008870:Microtubules / Q000378:metabolism*; D054730:Protein Interaction Domains and Motifs; D017434:Protein Structure, Tertiary; D014404:Tubulin / Q000378:metabolism
chemical_list: D008869:Microtubule-Associated Proteins; C401398:TUBGCP4 protein, human; D014404:Tubulin