Fig. 8.

Schematic representation showing binding surfaces of TREM2 in soluble and membrane-bound form. Aβ fibrils primarily bind along surface 2, which is away and distinct from surface 1 that houses the R47H mutation and plays a role in cellular binding and uptake. The membrane-bound form of TREM2 is attached to the membrane via a transmembrane helix and a flexible extracellular sequence. This membrane-bound form mediates signal transduction through the adapter protein DAP12 when TREM2 binds to polyvalent ligands that induce clustering of the DAP12 subunits.