Analysis of GlyR–Gly/IVM structures.a TEVC recording of 1 mM glycine-induced currents in the presence and absence of 0.5 μM IVM (left). Representative trace from multiple independent oocyte recordings (n = 5). The traces are normalized to the peak current to show the current decay. Ion permeation pathway for GlyR–Gly/IVM-1 GlyR–Gly/IVM-2 (right). Green and purple spheres define radii of 1.8–3.3 Å and >3.3 Å, respectively. The residues located at various pore constrictions are shown as sticks. b Current recording for 0.1 mM glycine and 0.1 mM glycine and 30 μM IVM (left). Representative trace from multiple independent oocyte recordings (n = 3). The pore profile for GlyR–Gly/IVM-3 structure. c A view of M2 helices from the extracellular end Positions Leu9′ and Pro-2′ and the corresponding distances between Cα in Å. d Alignment of GlyR structures showing the conformational differences at the level of Pro-2′. Dotted arrows indicate the direction of rotation going from the GlyR–Apo (closed) to the GlyR–Gly (desensitized) state.
|