S100A1 and Calmodulin Compete for the Same Binding Site on Ryanodine Receptor

In heart and skeletal muscle an S100 protein family member, S100A1, binds to the ryanodine receptor (RyR) and promotes Ca2+ release. Using competition binding assays, we further characterized this system in skeletal muscle and showed that Ca2+-S100A1 competes with Ca2+-calmodulin (CaM) for the same...

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Published inThe Journal of biological chemistry Vol. 283; no. 39; pp. 26676 - 26683
Main Authors Wright, Nathan T., Prosser, Benjamin L., Varney, Kristen M., Zimmer, Danna B., Schneider, Martin F., Weber, David J.
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 26.09.2008
American Society for Biochemistry and Molecular Biology
Subjects
Animals
Binding Sites - physiology
Calcium - chemistry
Calcium - metabolism
Calmodulin - chemistry
Calmodulin - genetics
Calmodulin - metabolism
Humans
Hydrophobic and Hydrophilic Interactions
Mice
Mice, Knockout
Models, Biological
Muscle Contraction - physiology
Muscle Proteins - chemistry
Muscle Proteins - genetics
Muscle Proteins - metabolism
Muscle, Skeletal - chemistry
Muscle, Skeletal - metabolism
Nuclear Magnetic Resonance, Biomolecular - methods
Peptides - chemistry
Peptides - genetics
Peptides - metabolism
Protein Structure and Folding
Protein Structure, Tertiary - physiology
Ryanodine Receptor Calcium Release Channel - chemistry
Ryanodine Receptor Calcium Release Channel - genetics
Ryanodine Receptor Calcium Release Channel - metabolism
S100 Proteins - chemistry
S100 Proteins - genetics
S100 Proteins - metabolism
Static Electricity
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Summary:In heart and skeletal muscle an S100 protein family member, S100A1, binds to the ryanodine receptor (RyR) and promotes Ca2+ release. Using competition binding assays, we further characterized this system in skeletal muscle and showed that Ca2+-S100A1 competes with Ca2+-calmodulin (CaM) for the same binding site on RyR1. In addition, the NMR structure was determined for Ca2+-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 Ca2+-S100A1. These same residues were shown previously to be important for RyR1 binding to Ca2+-CaM. A model for regulating muscle contraction is presented in which Ca2+-S100A1 and Ca2+-CaM compete directly for the same binding site on the ryanodine receptor.
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Supported in part by American Heart Association Fellowship 0615343U.
The atomic coordinates and structure factors (code 2K2F) have been deposited in the Protein Data Bank, Research Collaboratory for Structural Bioinformatics, Rutgers University, New Brunswick, NJ (http://www.rcsb.org/).
Supported in part by National Institutes of Health Grant T32 AR007592 (training grant) from NIAMS to the Interdisciplinary Program in Muscle Biology, University of Maryland School of Medicine.
This work was supported, in whole or in part, by National Institutes of Health Grants GM58888 and CA107331 (to D. J. W.) and AR055099 (to M. F. S.). The NMR spectrometers used in these studies were purchased, in part, by Shared Instrumentation Grants S10 RR10441, S10 RR15741, S10 RR16812, and S10 RR23447 (to D. J. W.) from the National Institutes of Health and DBI 0115795 from the National Science Foundation (to D. J. W.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M804432200