Computational Study of the Impact of the L483Y Mutation on the Desensitization of the AMPA Receptor

Abstract

with a conformational selection mechanism for binding. These results are also consistent with PMFs for NMDA but not AMPA receptor LBDs. Additionally, the open-cleft conformation is more accessible to the GluK2 apo state than the glutamate-bound state, consistent with previous results for both NMDA and AMPA receptors. Small-angle X-ray scattering profiles for the apo-and glutamate-bound states calculated from a Boltzmann-weighted ensemble of conformations are compared with experimental SAXS profiles. Finally, structural and biochemical properties of GluK2 in its apo state are probed using proteolytic protection assays, circular dichroism, and multi-angle light scattering.