A Mechano-chemical Model for γTuRC-mediated Microtubule Nucleation

Nucleation by the γ-tubulin ring complex (γTuRC) is the primary mechanism for microtubule (MT) multiplication in cells, yet its mechanism remains poorly understood—the prevailing template activation model cannot explain key experimental observations. We present a structure-based mechano-chemical model that integrates MT dynamic instability with a two-step open-to-closed transition of γTuRC. Closure resembles the MT sheet-to-tube transition, but with cone rather than tube geometry. The first step requires straightening of γ-tubulin complex proteins (GCPs), enabling lateral bonding between α,β-tubulin subunits bound to γ-tubulins, which supports sheet growth from γTuRC, suppressing catastrophe and promoting persistent elongation. The second step involves lateral rotation of GCPs and a bent-to-straight transition of γ-tubulins, driving sheet-to-tube conversion and yielding longer, more stable MTs and ensuring efficient nucleation. Simulations reproduce all recent in vitro results on γTuRC-mediated nucleation and reveal the underlying mechanism as an ordered sequence of conformational changes in GCPs and α, β, γ-tubulins.