fig1

Figure 1. RET missense mutations and structure. A: distribution of missense mutations mapped to the RET protein. Data were based on the curated dataset of cBioportal that contains results from 176 non-redundant studies that have 46,612 samples from 44,284 patients. Locations of the CLD and CRD domains are based on the 3D structure determined by cryo-EM (PDB: 6Q2N)^[3]; B: structure of RET/GFRα1/GDNF complex based on PDB 6Q2N. Disulfide bonds in CRD and in GDNF are shown in blue; C: the RET kinase domain structure (PDB: 6NJA)^[27]. AS: activating segment; V804 and K758: gate residues; Y806: hinge residue; G810: solvent front residue; M918 and A883: two of MTC-associated mutation residues; RET: rearranged during transfection; CLD: cadherin-like domains; CRD: cysteine-rich domain; GDNF: glial cell-derived neurotrophic factor