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  • 标题:A model of the glycine receptor deduced from Brownian dynamics studies
  • 本地全文:下载
  • 作者:Megan O'Mara ; Peter H. Barry ; Shin-Ho Chung
  • 期刊名称:Proceedings of the National Academy of Sciences
  • 印刷版ISSN:0027-8424
  • 电子版ISSN:1091-6490
  • 出版年度:2003
  • 卷号:100
  • 期号:7
  • 页码:4310-4315
  • DOI:10.1073/pnas.0630652100
  • 语种:English
  • 出版社:The National Academy of Sciences of the United States of America
  • 摘要:We have developed a three-dimensional model of the 1 homomeric glycine receptor by using Brownian dynamics simulations to account for its observed physiological properties. The model channel contains a large external vestibule and a shallow internal vestibule, connected by a narrow, cylindrical selectivity filter. Three rings of charged residues from the pore-lining M2 domain are modeled as point charges in the protein. Our simulations reproduce many of the key features of the channel, such as the current-voltage profiles, permeability ratios, and ion selectivity. When we replace the ring of alanine residues lining the selectivity filter with glutamates, the mutant model channel becomes permeable to cations, as observed experimentally. In this mutation, anions act as chaperones for sodium ions in the extracellular vestibule, and together they penetrate deep inside the channel against a steep energy barrier encountered by unaccompanied ions. Two subsequent amino acid mutations increase the cation permeability, enabling monovalent cations to permeate through the channel unaided and divalent cations to permeate when chaperoned by anions. These results illustrate the key structural features and underlying mechanism for charge selectivity in the glycine receptor.
  • 关键词:ligand-gated ion channels‖conductance‖permeation
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