Fig. 1.

Complex of PLCγ1 and the intracellular part of FGFR1. (a) Domain organisation of PLCγ1 and FGFR1 intracellular region (FGFRint). The PLC-core domains (nPH, EF-hands, TIM-barrel and C2 domain) and regulatory domains unique for PLCγ (spPH, nSH2, cSH2 and SH3, comprising a γ-specific array - γSA) are coloured dark and light blue, respectively. The FGFRint kinase domain is coloured orange. (b) Representative cryoEM micrograph collected on a Krios microscope fitted with a Volta phase plate and Falcon 3 detector. (c) Representative 2D classes generated with Relion. (d) Different views of the 3D map presented as mesh. (e) Architecture of the PLCγ1/FGFR1int complex with individual domains docked into the 3D map. (f) Model of the complex with the domains represented as cartoon and surface. The orientation of the model where the crosslinks (black dotted lines) between the domains in the PLC-core (dark blue) and the regulatory region (light blue) can be visualised is shown at the top. All crosslinks are within the restraints described in (Bullock et al., 2018). The model presented in the same orientation as in (e) is shown at the bottom. The positions of the most frequent PLCγ mutations discovered in different pathologies, are indicated using PLCγ1 numbering as red dots. Residues R687, L868 and S729 correspond to R665, L845 and S707 in PLCγ2 and are the most frequently mutated in the latter isoform. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)