Interaction of ions with the luminal sides of wild-type and mutated skeletal muscle ryanodine receptors

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• 作者：Roman Schilling ; Rainer H. A. Fink ; Wolfgang B. Fischer
• 关键词：RyR1 ; Ion channel ; Calcium ; Molecular dynamics simulations ; Ion dynamics
• 刊名：Journal of Molecular Modeling
• 出版年：2016
• 出版时间：January 2016
• 年：2016
• 卷：22
• 期：1
• 全文大小：3,104 KB
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• 作者单位：Roman Schilling (1)
  Rainer H. A. Fink (1)
  Wolfgang B. Fischer (2) (3)
  
  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, 155, Li-Non St., Sec. 2, Taipei, 112, Taiwan
  3. Biophotonics & Molecular Imaging Research Center (BMIRC), National Yang-Ming University, Taipei, 112, Taiwan
  
• 刊物类别：Chemistry and Materials Science
• 刊物主题：Chemistry
  Computer Applications in Chemistry
  Biomedicine
  Molecular Medicine
  Health Informatics and Administration
  Life Sciences
  Computer Application in Life Sciences
  
• 出版者：Springer Berlin / Heidelberg
• ISSN：0948-5023

文摘

Ryanodine receptors (RyRs) are the largest known ion channels, and are of central importance for the release of Ca2+ from the sarco/endoplasmic reticulum (SR/ER) in a variety of cells. In cardiac and skeletal muscle cells, contraction is triggered by the release of Ca2+ into the cytoplasm and thus depends crucially on correct RyR function. In this work, in silico mutants of the RyR pore were generated and MD simulations were conducted to examine the impact of the mutations on the Ca2+ distribution. The Ca2+ distribution pattern on the luminal side of the RyR was most affected by G4898R, D4899Q, E4900Q, R4913E, and D4917A mutations. MD simulations with our wild-type model and various ion species showed a preference for Ca2+ over other cations at the luminal pore entrance. This Ca2+-accumulating characteristic of the luminal RyR side may be essential to the conductance properties of the channel.