Kinde Monica N, Chen Qiang, Lawless Matthew J, Mowrey David D, Xu Jiawei, Saxena Sunil, Xu Yan, Tang Pei
Department of Anesthesiology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15260, USA.
Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Structure. 2015 Jun 2;23(6):995-1004. doi: 10.1016/j.str.2015.03.017. Epub 2015 May 7.
Structural rearrangements underlying functional transitions of pentameric ligand-gated ion channels (pLGICs) are not fully understood. Using (19)F nuclear magnetic resonance and electron spin resonance spectroscopy, we found that ELIC, a pLGIC from Erwinia chrysanthemi, expanded the extracellular end and contracted the intracellular end of its pore during transition from the resting to an apparent desensitized state. Importantly, the contraction at the intracellular end of the pore likely forms a gate to restrict ion transport in the desensitized state. This gate differs from the hydrophobic gate present in the resting state. Conformational changes of the TM2-TM3 loop were limited to the N-terminal end. The TM4 helices and the TM3-TM4 loop appeared relatively insensitive to agonist-mediated structural rearrangement. These results indicate that conformational changes accompanying functional transitions are not uniform among different ELIC regions. This work also revealed the co-existence of multiple conformations for a given state and suggested asymmetric conformational arrangements in a homomeric pLGIC.
五聚体配体门控离子通道（pLGICs）功能转变背后的结构重排尚未完全明确。通过¹⁹F核磁共振和电子自旋共振光谱，我们发现来自菊欧文氏菌的pLGIC——ELIC，在从静息态转变为明显脱敏态的过程中，其孔道的胞外端扩张而胞内端收缩。重要的是，孔道胞内端的收缩可能形成一个门，在脱敏态下限制离子运输。这个门不同于静息态存在的疏水门。TM2 - TM3环的构象变化仅限于N端。TM4螺旋和TM3 - TM4环对激动剂介导的结构重排相对不敏感。这些结果表明，不同ELIC区域伴随功能转变的构象变化并不一致。这项工作还揭示了给定状态下多种构象的共存，并提示同聚体pLGIC中存在不对称的构象排列。
