Key result
Calmodulin binds cardiac RyR2 via entropic drive alone, unlike dual enthalpy-entropy binding in RyR1.
Why the study?
The skeletal muscle RyR1 and cardiac muscle RyR2 ryanodine receptor channels share a conserved calmodulin binding domain but are differentially regulated by calmodulin, and their binding thermodynamics require clarification.
Highlights thermodynamic distinctions in CaM-RyR binding by isoform; leaves open whether these differences modulate excitation-contraction coupling in skeletal versus cardiac muscle.
The skeletal muscle (RyR1) and cardiac muscle (RyR2) ryanodine receptor calcium release channels contain a single, conserved calmodulin (CaM) binding domain, yet are differentially regulated by CaM. Here, we report that high-affinity [(35)S]CaM binding to RyR1 is driven by favorable enthalpic and entropic contributions at Ca(2+) concentrations from <0.01 to 100 microM. At 0.15 microM Ca(2+), [(35)S]CaM bound to RyR2 with decreased affinity and binding enthalpy compared with RyR1. The rates of [(35)S]CaM dissociation from RyR1 increased as the temperature was raised, whereas at 0.15 microM Ca(2+) the rate from RyR2 was little affected. The results suggest major differences in the energetics of CaM binding to and dissociation from RyR1 and RyR2.
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Meissner et al. (2008) studied this question. Calmodulin vs. RyR1 vs RyR2 was evaluated on Thermodynamic parameters of calmodulin binding and dissociation. Calmodulin binding to skeletal muscle RyR1 is driven by favorable enthalpy and entropy, whereas binding to cardiac muscle RyR2 is primarily entropically driven with an enthalpy near zero.
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