Energetics and Ion permeation Characteristics in a Glutamate-Gated Chloride (GluCl) Receptor Channel
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- 作者：Mary Hongying Cheng ; Rob D. Coalson
- 刊名：The Journal of Physical Chemistry B
- 出版年：2012
- 出版时间：November 26, 2012
- 年：2012
- 卷：116
- 期：46
- 页码：13637-13643
- 全文大小：433K
- 年卷期：v.116,no.46(November 26, 2012)
- ISSN：1520-5207
文摘
An invertebrate glutamate-gated chloride channel (GluCl) has recently been crystallized in an open-pore state. This channel is homologous to the human Cys-loop receptor family of pentameric ligand-gated ion channels, including anion-selective GlyR and GABAR and cation-selective nAChR and 5HT3. We implemented molecular dynamics (MD) in conjunction with an elastic network model to perturb the X-ray structure of GluCl and investigated the open channel stability and its ion permeation characteristics. Our study suggests that TM2 helical tilting may close GluCl near the hydrophobic constriction L254 (L9鈥?, similar to its cation-selective homologues. Ion permeation characteristics were determined by Brownian dynamics simulations using a hybrid MD/continuum electrostatics approach to evaluate the free energy profiles for ion transport. Near the selectivity filter region (P243 or P-2鈥?, the free energy barrier for Na+ transport is over 4 kBT higher than that for Cl鈥?/sup>, indicating anion selectivity of the channel. Furthermore, three layers of positivity charged rings in the extracellular domain also contribute to charge selectivity and facilitate Cl鈥?/sup> permeability over Na+. Collectively, the charge selectivity of GluCl may be determined by overall electrostatic and ion dehydration effects, perhaps not deriving from a single region of the channel (the selectivity filter region near the intracellular entrance).