title: S100A1 and calmodulin compete for the same binding site on ryanodine receptor.
abstract: In heart and skeletal muscle an S100 protein family member, S100A1, binds to the ryanodine receptor (RyR) and promotes Ca(2+) release. Using competition binding assays, we further characterized this system in skeletal muscle and showed that Ca(2+)-S100A1 competes with Ca(2+)-calmodulin (CaM) for the same binding site on RyR1. In addition, the NMR structure was determined for Ca(2+)-S100A1 bound to a peptide derived from this CaM/S100A1 binding domain, a region conserved in RyR1 and RyR2 and termed RyRP12 (residues 3616-3627 in human RyR1). Examination of the S100A1-RyRP12 complex revealed residues of the helical RyRP12 peptide (Lys-3616, Trp-3620, Lys-3622, Leu-3623, Leu-3624, and Lys-3626) that are involved in favorable hydrophobic and electrostatic interactions with Ca(2+)-S100A1. These same residues were shown previously to be important for RyR1 binding to Ca(2+)-CaM. A model for regulating muscle contraction is presented in which Ca(2+)-S100A1 and Ca(2+)-CaM compete directly for the same binding site on the ryanodine receptor.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
authors.forename: Nathan T
authors.initials: NT
authors.lastname: Wright
authors.forename: Benjamin L
authors.initials: BL
authors.lastname: Prosser
authors.forename: Kristen M
authors.initials: KM
authors.lastname: Varney
authors.forename: Danna B
authors.initials: DB
authors.lastname: Zimmer
authors.forename: Martin F
authors.initials: MF
authors.lastname: Schneider
authors.forename: David J
authors.initials: DJ
authors.lastname: Weber
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000502:physiology; D002118:Calcium / Q000737:chemistry / Q000378:metabolism*; D002147:Calmodulin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D009119:Muscle Contraction / Q000502:physiology*; D009124:Muscle Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000737:chemistry / Q000378:metabolism*; D019906:Nuclear Magnetic Resonance, Biomolecular / Q000379:methods; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary / Q000502:physiology; D019837:Ryanodine Receptor Calcium Release Channel / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009418:S100 Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D055672:Static Electricity
chemical_list: D002147:Calmodulin; D009124:Muscle Proteins; D010455:Peptides; D019837:Ryanodine Receptor Calcium Release Channel; D009418:S100 Proteins; C110294:S100A1 protein; D002118:Calcium