An exTREMe disruption in Alzheimer`s cleanup [Protein Structure and Folding] (Journal of Biological Chemistry)

Partial loss-of-function variants in the TREM2 immune receptor are associated with increased risk for Alzheimer`s disease (AD) and other forms of neurodegenerative disease, but the molecular bases for these connections are unknown. Three new structures of WT and R47H mutant TREM2 immunoglobulin-like (Ig-like) domain now reveal that R47 functions to correctly position elements of the ligand-binding surface. Intriguingly, the authors also demonstrate a disruption of receptor oligomerization by the R47H mutation, suggesting a role for ligand-induced clustering in receptor signaling and resultant plaque clearance.