S100A1 and calmodulin compete for the same binding site on ryanodine receptor.

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TitleS100A1 and calmodulin compete for the same binding site on ryanodine receptor.
Publication TypeJournal Article
Year of Publication2008
AuthorsWright, NT, Prosser, BL, Varney, KM, Zimmer, DB, Schneider, MF, Weber, DJ
JournalJ Biol Chem
Volume283
Issue39
Pagination26676-83
Date Published2008 Sep 26
ISSN0021-9258
KeywordsAnimals, Binding Sites, Calcium, Calmodulin, Humans, Hydrophobic and Hydrophilic Interactions, Mice, Mice, Knockout, Models, Biological, Muscle Contraction, Muscle Proteins, Muscle, Skeletal, Nuclear Magnetic Resonance, Biomolecular, Peptides, Protein Structure, Tertiary, Ryanodine Receptor Calcium Release Channel, S100 Proteins, Static Electricity
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.

DOI10.1074/jbc.M804432200
Alternate JournalJ. Biol. Chem.
PubMed ID18650434
PubMed Central IDPMC2546546
Grant ListAR055099 / AR / NIAMS NIH HHS / United States
CA107331 / CA / NCI NIH HHS / United States
GM58888 / GM / NIGMS NIH HHS / United States
S10 RR10441 / RR / NCRR NIH HHS / United States
S10 RR15741 / RR / NCRR NIH HHS / United States
S10 RR16812 / RR / NCRR NIH HHS / United States
S10 RR23447 / RR / NCRR NIH HHS / United States
T32 AR007592 / AR / NIAMS NIH HHS / United States