Sobolevsky Alexander I, Yelshansky Maria V, Wollmuth Lonnie P
Department of Neurobiology and Behavior, State University of New York at Stony Brook, Stony Brook, NY 11794, USA.
Neuron. 2004 Feb 5;41(3):367-78. doi: 10.1016/s0896-6273(04)00008-x.
The ligand binding domain of glutamate receptors (GluRs) has 2-fold rotational symmetry. The structure including the symmetry of the GluR ion channel remains undefined. Here we used substituted cysteines in the pore-lining M3 segment of the AMPAR GluR-A subunit and various cysteine-reactive agents to study the structure of the channel during gating. We find that cysteines substituted at A+6, located in the highly conserved SYTANLAAF motif, are grouped in pairs consistent with a 2-fold symmetry in the extracellular part of the pore. To account for this symmetry and crosslinking, we propose that the M3 segments in two neighboring GluR subunits are kinked within SYTANLAAF in opposite directions relative to the central axis of the pore. Our results extend the 2-fold rotational symmetry from the ligand binding domain to at minimum the extracellular part of the channel and suggest a model of gating movements in GluR pore-forming domains.
谷氨酸受体（GluRs）的配体结合结构域具有二重旋转对称性。包括GluR离子通道对称性在内的结构仍不明确。在此，我们利用AMPA受体GluR - A亚基孔道内衬M3片段中的取代半胱氨酸以及各种半胱氨酸反应试剂，来研究门控过程中通道的结构。我们发现，位于高度保守的SYTANLAAF基序中的A + 6位点处取代的半胱氨酸，两两成组，这与孔道胞外部分的二重对称性一致。为了解释这种对称性和交联现象，我们提出，两个相邻GluR亚基中的M3片段在SYTANLAAF基序内相对于孔道中心轴沿相反方向发生扭结。我们的研究结果将二重旋转对称性从配体结合结构域扩展至至少通道的胞外部分，并提出了GluR孔道形成结构域中的门控运动模型。
