Fig. 3: Memantine block revealed by Cryo-EM.
A Overall architecture of GluA2-γ2mem in a ribbon diagram. GluA2 subunits are labeled depending on their positions (A, C are green; B, D are pink). γ2 subunits are colored white. Dashed lines indicate domain boundaries, solid bars indicate membrane boundaries. Glutamate (yellow), CTZ (purple), and memantine (cyan) are shown as space filling models. Inset i is where (B) highlights. B The GluA2-γ2mem ion channel with M2 and M3 helices. Subunit C is omitted for clarity. The cryo-EM map at the memantine binding site is shown transparently in cyan around the molecule. Critical binding residues are labeled. Carbon atoms are colored with the color of their respective subunit with oxygen in red, nitrogen in blue. C LigPlot of the memantine binding site. Potential polar contacts are indicated with purple eyelashes. Orange eyelashes indicate a distance within 4 Å from memantine. Yellow eyelashes indicate a distance from 4 to 6 Å. D How memantine rearranges the Q/R site; cyan arrows indicate changes from GluA2-γ2open (purple) to GluA2-γ2mem (green). E Pore radius plots of GluA2-γ2open (purple) and GluA2-γ2mem (green). Dashed line represents the radius of a calcium cation.
