MD simulations of the central pore of ryanodine receptors and sequence comparison with 2B protein from coxsackie virus

The regulation of intracellular Ca^{2 +} triggers a multitude of vital processes in biological cells. Ca^{2 +} permeable ryanodine receptors (RyRs) are the biggest known ion channels and play a key role in the regulation of intracellular calcium concentrations, particularly in muscle cells. In this study, we construct a computational model of the pore region of the skeletal RyR and perform molecular dynamics (MD) simulations. The dynamics and distribution of Ca^{2 +} around the luminal pore entry of the RyR suggest that Ca^{2 +} ions are channeled to the pore entry due to the arrangement of (acidic) amino acids at the extramembrane surface of the protein. This efficient mechanism of Ca^{2 +} supply is thought to be part of the mechanism of Ca^{2 +} conductance of RyRs. Viral myocarditis is predominantly caused by coxsackie viruses that induce the expression of the protein 2B which is known to affect intracellular Ca^{2 +} homeostasis in infected cells. From our sequence comparison, it is hypothesized, that modulation of RyR could be due to replacement of its transmembrane domains (TMDs) by those domains of the viral channel forming protein 2B of coxsackie virus. This article is part of a Special Issue entitled: Viral Membrane Proteins - Channels for Cellular Networking.