Fig. 3.

IGF1 binding site in the active-IGF1R dimer. a Close-up view of the interaction between IGF1R and IGF1 in two orthogonal views. b IGF1-induced IGF1R autophosphorylation in 293FT cells expressing WT IGF1R or indicated mutants. The kinase dead mutant (D1105N) was used as a negative control. c Quantification of the western blot data shown in b (Mean ± SD). Each experiment was repeated five times. Significance calculated using two-tailed students t-test; between WT and mutants; **p < 0.01, ***p < 0.001, and ****p < 0.0001. d IGF1-induced IGF1R autophosphorylation in 293FT cells expressing WT IGF1R or indicated mutants. e Quantification of the western blot data shown in d (Mean ± SD). Each experiment was repeated four times. Significance calculated using two-tailed students t-test; **p < 0.01 and ***p < 0.001. f Domain organization of IGF1. g Superposition between apo-IGF1 (gray) and IGF1 after binding IGF1R (pink), revealing the conformational change of C-domain (indicated by the arrow). h Sequence alignment of human IGF1, mouse IGF1, human IGF2, and insulin, showing the non-conserved C-domain. i Superposition between IGF1-bound IGF1R (pink and orange) and Insulin-bound IR (dark gray and light gray). Source data are provided as a Source Data file