Figure 9.
Sedimentation equilibrium data showing that CX614 and aniracetam stabilize the GluR2 dimer to different extents. A, Sedimentation equilibrium data taken in the presence of 0.3 mm AMPA and 0.3 mm CX614; the data shown here was collected at 27 K rpm and a protein concentration of 1.0 mg/ml. B, Sedimentation equilibrium data measured in the presence of 2 mm glutamate and 5 mm aniracetam. For the data shown here, the rotor speed was also 27 K rpm, and the loading protein concentration was 0.75 mg/ml. In both of the experiments involving CX614 and aniracetam, interference data from three loading protein concentrations and three rotor speeds were fit to a dimer–monomer equilibrium, yielding a protein dimer Kd of 26.1 μm in the case of CX614 and 1.4 mm for aniracetam. InA and B, the top panels show the residuals of the fit of the dimer–monomer model to the measured interference data, and the bottom panels show the measured interference data (open black circles), the fit to the data (solid black line), and the relative predicted concentrations of dimer (dark gray line) and monomer (light gray line). As seen in A, CX614 is much more effective in shifting the dimer–monomer toward dimer than aniracetam.