Abstract
Ryanodine receptors (RyRs) are large ion channels that are responsible for the release of Ca(2+) from the sarcoplasmic/endoplasmic reticulum. Calmodulin (CaM) is a Ca(2+) binding protein that can affect the channel open probability at both high and low Ca(2+) concentrations, shifting the Ca(2+) dependencies of channel opening in an isoform-specific manner. Here we analyze the binding of CaM and its individual domains to three different RyR regions using isothermal titration calorimetry. We compared binding to skeletal muscle (RyR1) and cardiac (RyR2) isoforms, under both Ca(2+)-loaded and Ca(2+)-free conditions. CaM can bind all three regions in both isoforms, but the binding modes differ appreciably in two segments. The results highlight a Ca(2+)/CaM and apoCaM binding site in the C-terminal fifth of the channel. This binding site is the target for malignant hyperthermia and central core disease mutations in RyR1, which affect the energetics and mode of CaM binding.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
