MD simulations of the central pore of ryanodine receptors and sequence comparison with 2B protein from coxsackie virus |
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| Authors: | Roman Schilling Rainer HA Fink Wolfgang B Fischer |
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| Institution: | 1. Medical Biophysics Group, Institute of Physiology and Pathophysiology, University of Heidelberg, 69120 Heidelberg, Germany;2. Institute of Biophotonics, School of Biomedical Science and Engineering, National Yang-Ming University, Taipei 112, Taiwan;3. Biophotonics & Molecular Imaging Research Center (BMIRC), National Yang-Ming University, Taipei 112, Taiwan |
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| Abstract: | The regulation of intracellular Ca2 + triggers a multitude of vital processes in biological cells. Ca2 + 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 Ca2 + around the luminal pore entry of the RyR suggest that Ca2 + 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 Ca2 + supply is thought to be part of the mechanism of Ca2 + 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 Ca2 + 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. |
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| Keywords: | Ryanodine receptor Ca homeostasis Molecular dynamics simulations Ion dynamics Viral channel proteins 2B of coxsackie virus |
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