Fig. 2

Structural insights relating to PLCγ2 and the AD protective mutation. a The domain structure of PLCγ2. The amino acid identities when compared to PLCγ1 for individual domains and some linkers are indicated. Also indicated are the positions of the P522R AD mutation, the Y759 and Y1217 residues potentially involved in enzyme regulation through phosphorylation. b Model of the structure of PLCγ2 prepared in the Schrödinger suite (Schrödinger Release 2018–3: Prime, Schrödinger, LLC, New York, NY, 2020) using the program Prime to predict loops [85, 86]. The homology model was built from the Uniprot sequence of PLCγ2 (P16885) and the PLCγ1 structure (pdb:6PBC) was used as template. c Front and top view of the PLCγ2 structural model with the following features indicated: autoinhibitory interface between the core, catalytic domains and the specific array domains (purple). The location of mutations identified in a range of pathologies (blue). The location of the protective AD mutation on the inter spPH-nSH2 linker (red)