Figure 2.Figure 2
Domain structure of the Trem2 protein and its association with Alzheimer disease (AD) risk. ( A ) Human Trem2 protein domain structure: this schematic illustrates the structural domains of the human Trem2 protein, including the signal peptide (SP), transmembrane domain (TM), and C-terminal tail (CT). Notable are the common variants associated with AD risk and the cleavage sites for ADAM17/10, which are crucial for Trem2’s functional modulation in the disease context. ( B ) Membrane-bound three-dimensional (3D) structure of Trem2-DAP12 complex: derived from AlphaFold (ID: Q9NZC2 ), this representation showcases the 3D conformation of Trem2 as it anchors to the cell membrane through a transmembrane helix. TREM2’s interaction with DAP12 (AlphaFold ID: O43914 ) is highlighted, showing electrostatic interactions (involving lysine and arginine residues) within the transmembrane domains. Additionally, the dimerization of two DAP12 proteins through a disulfide bond is depicted, emphasizing t