What they found

Characterization of calcineurin’s dual Ca²⁺-sensing mechanism: calmodulin binding to the CaM-binding domain increases catalytic rate and modulates Ca²⁺ response; calcineurin B (regulatory subunit) sets baseline Ca²⁺ sensitivity. Together they produce highly cooperative Ca²⁺ activation (Hill n = 2.8–3). Half-maximum Ca²⁺ concentration for activation: 0.6–1.3 µM depending on CaM concentration.

Numbers that matter

  • Ca²⁺ for half-max calcineurin activation: 0.6–1.3 µM (model Kd_CaN = 500 nM is slightly below range — a minor underestimate)
  • Hill coefficient: 2.8–3 (model n_CaN_Hill = 4.0 is slightly steeper than measured)
  • CaM increases catalytic turnover rate ~10-fold at saturating Ca²⁺
  • Calcineurin B shifts Ca²⁺ sensitivity to lower concentrations

Fit to h05

The RBM24 ODE model uses Kd_CaN = 500 nM and n_CaN_Hill = 4.0. Stemmer & Klee 1994 gives 600–1300 nM and Hill n = 2.8–3. Both values deviate modestly: Kd is ~20% low (conservative — makes CaN activate earlier), Hill n is ~35% steep (makes CaN more switch-like). Neither is a fatal error for the qualitative CaMKII:CaN decoding hypothesis.

Connections