Effect of Experimental Drug S107 on Accessory Protein Binding to the RyR
2012-04-18
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Effect of Experimental Drug S107 on Accessory Protein Binding to the RyR
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2012-04-18
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The physiological basis of muscle-generated motor activity depends on the precise regulation of intracellular Ca2+ ions. Central to this process is the sarcoplasmic reticulum (SR), a special organelle in muscle cells that is responsible for ion storage. The Ca2+ ions are released from the SR through a large conductance channel known as the ryanodine receptor (RyR). The channel’s activity is in turn regulated by intracellular messengers, including FK506 binding proteins (FKBP12.6 & 12.0), and calmodulin (CaM). The experimental heart failure drug S107 has been associated with improved muscle performance, though it is still unclear if it directly affects the binding activity of either the FKBPs or CaM. Here, the effect of S107 on the binding of fluorescent FKBPs and CaM to RyR is characterized. The results show that S107 slightly, but significantly, decreases the binding affinity of CaM; though, only in nanomolar calcium concentrations, and when the RyR is treated with oxidized glutathione. S107 has no significant effect on the binding of FKBP to RyR. Prior to this research, it was thought that S107 might significantly increase the binding affinity of FKBP. The effect of S107 on CaM binding to RyR has not been previously investigated. These results suggest that the primary mechanism through which S107 achieves its physiological effects does not require or affect FKBP binding. Further studies will have to determine whether the effect of S107 on CaM binding to RyR is linked to the inhibition of Ca2+ leak in the channel.
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Faculty adviser: Razvan Cornea
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This research was supported by the Undergraduate Research Opportunities Program (UROP). Also, National Institutes of Health (Grant HL92097)
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Popa, Mircea Anton. (2012). Effect of Experimental Drug S107 on Accessory Protein Binding to the RyR. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/123409.
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