title: Thermodynamics of calmodulin binding to cardiac and skeletal muscle ryanodine receptor ion channels.
abstract: 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.
authors.affiliation: Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, North Carolina 27599-7260, USA. meissner@med.unc.edu
authors.forename: Gerhard
authors.initials: G
authors.lastname: Meissner
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Pasek
authors.forename: Naohiro
authors.initials: N
authors.lastname: Yamaguchi
authors.forename: Srinivas
authors.initials: S
authors.lastname: Ramachandran
authors.forename: Nikolay V
authors.initials: NV
authors.lastname: Dokholyan
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Tripathy
mesh_terms: 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
chemical_list: D002147:Calmodulin; D019837:Ryanodine Receptor Calcium Release Channel; D002118:Calcium