Key result
Removal of negative charges in the RyR1 Ca2+-binding site impairs RyR1 activation by physiological Ca2+ concentrations and results in loss of binding to Ca2+ or reduced Ca2+ affinity.
Population
HEK293 cells expressing skeletal-muscle ryanodine receptor ion channel (RyR1) variants
Comparison
Mutational replacement of three amino acid… vs Wild-type RyR1 (WT-RyR1)
Design
Preclinical
Authors
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Mutational data on RyR1 Ca2+ site are hypothesis-generating; leaves open physiologic or therapeutic relevance in muscle disorders.
Electrostatic interactions between Ca2+ and negatively charged glutamate residues in the RyR1 Ca2+-binding site are critical for channel activation by physiological Ca2+ concentrations.
Xu et al. (2018) studied Skeletal muscle RyR1 function. Mutational replacement of amino acid residues in RyR1 Ca2+-binding site vs. WT-RyR1 was evaluated on Activation by Ca2+. Removal of negative charges in the RyR1 Ca2+-binding site impairs RyR1 activation by physiological Ca2+ concentrations and results in loss of binding to Ca2+ or reduced Ca2+ affinity.
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