School of Biomedical, Biomolecular and Chemical Sciences, The University of Western Australia, Crawley, Western Australia.
Biophys J. 2010 Feb 3;98(3):404-11. doi: 10.1016/j.bpj.2009.10.032.
Four x-ray crystal structures of prokaryotic homologs of ligand-gated ion channels have recently been determined: ELIC from Erwinia chrysanthemi, two structures of a proton-activated channel from Gloebacter violaceus (GLIC1 and GLIC2) and that of the E221A mutant (GLIC1M). The availability of numerous structures of channels in this family allows for aspects of channel gating and ion conduction to be examined. Here, we determine the likely conduction states of the four structures as well as IV curves, ion selectivity, and steps involved in ion permeation by performing extensive Brownian dynamics simulations. Our results show that the ELIC structure is indeed nonconductive, but that GLIC1 and GLIC1M are both conductive of ions with properties different from those seen in experimental studies of the channel. GLIC2 appears to reflect an open state of the channel with a predicted conductance of 10.8-12.4 pS in 140 mM NaCl solution, which is comparable to the experimental value 8 +/- 2 pS. The extracellular domain of the channel is shown to have an important influence on the channel current, but a less significant role in ion selectivity.
最近已经确定了四个原核配体门控离子通道同源物的 X 射线晶体结构：来自欧文氏菌的 ELIC、来自 Gloebacter violaceus 的两个质子激活通道的结构（GLIC1 和 GLIC2）以及 E221A 突变体（GLIC1M）。该家族中大量通道结构的可用性使得可以检查通道门控和离子传导的各个方面。在这里，我们通过进行广泛的布朗动力学模拟来确定这四个结构的可能传导状态以及 IV 曲线、离子选择性以及离子渗透所涉及的步骤。我们的结果表明，ELIC 结构确实是不可传导的，但 GLIC1 和 GLIC1M 都能传导离子，其性质与通道实验研究中观察到的不同。GLIC2 似乎反映了通道的开放状态，在 140mM NaCl 溶液中的预测电导率为 10.8-12.4pS，与实验值 8 +/- 2pS 相当。通道的细胞外结构域被证明对通道电流有重要影响，但对离子选择性的作用较小。
