A model of the glycine receptor deduced from Brownian dynamics studies

O'Mara, Megan, Barry, Peter H. and Chung, Shin-Ho (2003) A model of the glycine receptor deduced from Brownian dynamics studies. Proceedings of the National Academy of Sciences of the United States of America, 100 7: 4310-4315. doi:10.1073/pnas.0630652100


Author O'Mara, Megan
Barry, Peter H.
Chung, Shin-Ho
Title A model of the glycine receptor deduced from Brownian dynamics studies
Journal name Proceedings of the National Academy of Sciences of the United States of America   Check publisher's open access policy
ISSN 1091-6490
Publication date 2003-04-01
Sub-type Article (original research)
DOI 10.1073/pnas.0630652100
Volume 100
Issue 7
Start page 4310
End page 4315
Total pages 6
Place of publication Washington, D.C., U.S.A.
Publisher National Academy of Sciences of the U.S.
Language eng
Subject 0304 Medicinal and Biomolecular Chemistry
Abstract We have developed a three-dimensional model of the α1 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.
Keyword Ligand-gated ion channel
Conductance
Permeation
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Unknown

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Chemistry and Molecular Biosciences
 
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Created: Thu, 07 Jan 2010, 12:23:47 EST by Therese Egan on behalf of Faculty of Science