Key result
ATP and caffeine regulate skeletal muscle ryanodine receptor (RyR1) activation through a network of allosteric interactions that modulate the conformation of the Ca2+-binding site.
Why the study?
Although binding sites for the coactivators Ca2+, ATP, and caffeine on RyR1 have been identified, the mechanism of coregulation and synergy among them remains to be determined.
Comparison
Activators alone vs in combination in the presence or absence of Ca2+
Design
In vitro ligand-binding assays and molecular dynamics simulations
Authors
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May guide RyR1 modulator design for muscle disorders; leaves open clinical translation pending in vivo data.
Chirasani et al. (2021) studied Skeletal muscle ryanodine receptor (RyR1) function. ATP and Caffeine vs. Absence of ATP/Caffeine was evaluated on [3H]ryanodine binding (RyR1 activation). ATP and caffeine regulate skeletal muscle ryanodine receptor (RyR1) activation through a network of allosteric interactions that modulate the conformation of the Ca2+-binding site.
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