Molecular Biology Commons^™

Characterization Of The Calmodulin-Ryanodine Receptor Interaction By Cryo-Electron Microscopy, Xiaojun Huang

Legacy Theses & Dissertations (2009 - 2024)

Ryanodine receptor (RyR) is a key player in excitation-contraction coupling (E-C coupling). Calmodulin (CaM) is one of the important regulatory factors of RyR. Two mammalian RyR isoforms, RyR1 and RyR2, are highly enriched in skeletal and cardiac muscle, respectively. Apo-calmodulin weakly activates RyR1 but inhibits RyR2, whereas Ca2+-calmodulin inhibits both the isoforms. Previous cryo-electron microscopy studies showed distinctly different binding locations on RyR1 for the two states of calmodulin. However, recent studies employing fluorescence resonance energy transfer appeared to challenge these findings. In chapter 1, using cryo-electron microscopy, we have determined that a mutant calmodulin, which is incapable of binding …