A structural model for the autoinhibition of the γ-TuRC-activating CM1 domain.

A conserved dimeric coiled-coil hairpin structure mediates autoinhibition of the CM1 domain, preventing γ-TuRC binding in humans and flies.

• Why it matters: Understanding how γ-TuRC activation is tightly regulated is crucial to prevent cell division errors, but the molecular basis of CM1 autoinhibition remained unknown.
• What they did: The study used structural approaches to reveal that CM1 forms a dimeric hairpin that sequesters a key phenylalanine residue, with additional autoinhibition in flies involving an upstream CAI domain.
• The result: This model clarifies the mechanism of CM1 autoinhibition, highlights evolutionary differences, and provides insights into controlling microtubule nucleation during cell division.