Figure 3

Proposed mechanism by which Q226E induces spontaneous activation. The TM1 and TM2 helices are coloured green and red, respectively, and are located in adjacent subunits. A. In the wild type (WT) α1 hGlyR, glycine induces activation by tilting the top of TM2 away from the pore axis towards TM1, where the open state is weakly stabilized by an H-bond between Q226 and R271. Hyperekplexia mutations at R271 are likely to disrupt this bond, thus destabilising the open state. B. In the Q226E mutant α1 hGlyR, a stable open state in the absence of glycine is induced via the formation of a strong electrostatic bond between Q226E and R271.