Life Sciences Commons^™

The Binding Properties And Functional Consequences Of Ryr2-Cam Interaction, Yi Yang

Dissertations

The aim of my dissertation is to understand the regulation of RyR2. The whole dissertation is composed of two parts. The first part focused on RyR2-CaM interaction. The second focused on synthetic RyR2 domain peptide (DPc10), which worked as a powerful molecular tool for RyR2 functional and structural studies.

CaM has been long identified as an important cardiac RyR regulator. Broad studies suggest CaM is a critical RyR2 stabilizer and CaM-RyR2 interaction is a critical molecular substrate for arrhythmias and HF pathogenesis, but the in situ binding properties for CaM-RyR2 are still unknown. Here we, Using FRET detection and permeabilized …

An Investigation Of The Phospholamban-Serca Regulatory Interaction With Fluorescence Resonance Energy Transfer, Philip Adam Bidwell

Dissertations

With Fluorescence Resonance Energy Transfer (FRET), we are able to detect changes in the structure and affinity of the PLB-SERCA regulatory complex in live cells. Using this approach, we have detected a high level of PLB-SERCA interaction even at Ca2+ concentrations known to fully relieve PLB inhibition of SERCA, suggesting that dissociation is not required for relief of inhibition. We also detect no real-time change in PLB-SERCA binding over the course of a single Ca2+ transient in paced myocytes. The effect of Ca2+ on the PLB-SERCA interaction is best described as a reduced affinity with no change in the structure …