Asymmetric Molecular Architecture of the Human ?-Tubulin Ring Complex.

ABSTRACT: The ?-tubulin ring complex (?-TuRC) is an essential regulator of centrosomal and acentrosomal microtubule formation, yet its structure is not known. Here, we present a cryo-EM reconstruction of the native human ?-TuRC at ?3.8 Å resolution, revealing an asymmetric, cone-shaped structure. Pseudo-atomic models indicate that GCP4, GCP5, and GCP6 form distinct Y-shaped assemblies that structurally mimic GCP2/GCP3 subcomplexes distal to the ?-TuRC "seam." We also identify an unanticipated structural bridge that includes an actin-like protein and spans the ?-TuRC lumen. Despite its asymmetric architecture, the ?-TuRC arranges ?-tubulins into a helical geometry poised to nucleate microtubules. Diversity in the ?-TuRC subunits introduces large (>100,000 Å²) surfaces in the complex that allow for interactions with different regulatory factors. The observed compositional complexity of the ?-TuRC could self-regulate its assembly into a cone-shaped structure to control microtubule formation across diverse contexts, e.g., within biological condensates or alongside existing filaments.

SUBMITTER: Wieczorek M 

PROVIDER: S-EPMC7027161 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature