Thermodynamics of calmodulin binding to cardiac and skeletal muscle ryanodine receptor ion channels.
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.
Meissner
Gerhard
G
Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, North Carolina 27599-7260, USA. meissner@med.unc.edu
Pasek
Daniel A
DA
Yamaguchi
Naohiro
N
Ramachandran
Srinivas
S
Dokholyan
Nikolay V
NV
Tripathy
Ashutosh
A
D002118:Calcium / Q000737:chemistry; D002147:Calmodulin / Q000378:metabolism*; D006801:Humans; D018482:Muscle, Skeletal / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D011485:Protein Binding; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism*; D013696:Temperature; D013816:Thermodynamics
D002147:Calmodulin; D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium