scholarly journals The Cardiac Ryanodine Receptor Phosphorylation Hotspot Embraces PKA in a Phosphorylation-Dependent Manner

2019 ◽  
Vol 75 (1) ◽  
pp. 39-52.e4 ◽  
Author(s):  
Omid Haji-Ghassemi ◽  
Zhiguang Yuchi ◽  
Filip Van Petegem
Keyword(s):  
Ryanodine Receptor ◽  
Dependent Manner ◽  
Receptor Phosphorylation ◽  
Cardiac Ryanodine Receptor

scholarly journals Ca2+-dependent calmodulin binding to cardiac ryanodine receptor (RyR2) calmodulin-binding domains

2019 ◽  
Vol 476 (2) ◽  
pp. 193-209 ◽  
Author(s):  
Malene Brohus ◽  
Mads T. Søndergaard ◽  
Sui Rong Wayne Chen ◽  
Filip van Petegem ◽  
Michael T. Overgaard
Keyword(s):  
Ryanodine Receptor ◽  
Fluorescence Anisotropy ◽  
Dependent Manner ◽  
Binding Model ◽  
Calmodulin Binding ◽  
Binding Domains ◽  
Wide Range ◽  
Dependent Inhibition ◽  
Life Threatening ◽  
Cardiac Ryanodine Receptor

Abstract The Ca2+ sensor calmodulin (CaM) regulates cardiac ryanodine receptor (RyR2)-mediated Ca2+ release from the sarcoplasmic reticulum. CaM inhibits RyR2 in a Ca2+-dependent manner and aberrant CaM-dependent inhibition results in life-threatening cardiac arrhythmias. However, the molecular details of the CaM–RyR2 interaction remain unclear. Four CaM-binding domains (CaMBD1a, -1b, -2, and -3) in RyR2 have been proposed. Here, we investigated the Ca2+-dependent interactions between CaM and these CaMBDs by monitoring changes in the fluorescence anisotropy of carboxytetramethylrhodamine (TAMRA)-labeled CaMBD peptides during titration with CaM at a wide range of Ca2+ concentrations. We showed that CaM bound to all four CaMBDs with affinities that increased with Ca2+ concentration. CaM bound to CaMBD2 and -3 with high affinities across all Ca2+ concentrations tested, but bound to CaMBD1a and -1b only at Ca2+ concentrations above 0.2 µM. Binding experiments using individual CaM domains revealed that the CaM C-domain preferentially bound to CaMBD2, and the N-domain to CaMBD3. Moreover, the Ca2+ affinity of the CaM C-domain in complex with CaMBD2 or -3 was so high that these complexes are essentially Ca2+ saturated under resting Ca2+ conditions. Conversely, the N-domain senses Ca2+ exactly in the transition from resting to activating Ca2+ when complexed to either CaMBD2 or -3. Altogether, our results support a binding model where the CaM C-domain is anchored to RyR2 CaMBD2 and saturated with Ca2+ during Ca2+ oscillations, while the CaM N-domain functions as a dynamic Ca2+ sensor that can bridge noncontiguous regions of RyR2 or clamp down onto CaMBD2.

Human Cardiac Ryanodine Receptor: Preparation, Crystallization and Preliminary X-ray Analysis of the N-terminal Region

2013 ◽  
Vol 20 (11) ◽  
pp. 1211-1216 ◽  
Author(s):  
L’ubomír Borko ◽  
Július Kostan ◽  
Alexandra Zahradníkova ◽  
Vladimír Pevala ◽  
Juraj Gasperík ◽  
...  
Keyword(s):  
Ryanodine Receptor ◽  
Terminal Region ◽  
X Ray ◽  
Cardiac Ryanodine Receptor

Antiarrhythmic Potential of Drugs Targeting the Cardiac Ryanodine Receptor Ca2+ Release Channel: Case Study of Dantrolene

2014 ◽  
Vol 21 (8) ◽  
pp. 1062-1072 ◽  
Author(s):  
Karoly Acsai ◽  
Norbert Nagy ◽  
Zoltan Marton ◽  
Kinga Oravecz ◽  
Andras Varro
Keyword(s):  
Ryanodine Receptor ◽  
Release Channel ◽  
Cardiac Ryanodine Receptor
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