Fig. 2: Structural details of DILP2 and DILP5 binding to the active dmIR.

Close-up view of the site-1 binding of DILP5 (a) and DILP2 (b) to dmIR. Site-1 DILP2 or DILP5 is shown in yellow, and two protomers of dmIR are shown in green and blue. c Structural comparison of dmIR/DILP5 and dmIR/DILP2 complexes. The structures of dmIR/DILP5 (gray) and dmIR/DILP2 (blue) are superimposed based on their site-1 ligand-binding site (L1–CR–L2 domains) and shown in ribbon representations. d Close-up view of the site-1′ and site-2 binding of DILP5 to dmIR. Site-1′ and site-2 DILP5 are shown in yellow and pink, respectively. Two protomers of dmIR are shown in green and blue. e Sequence alignment of the B- and A-chains of DILP2 and DILP5. Color code: dark blue, conserved residues; light blue, similar residues. The green box highlights the “DFR” motif on the N-terminus of A-chain of DILP5 that is important for the site-1′ binding, and the dotted red boxes highlight the DILP5 residues involved in site-2 binding to dmIR. f Autophosphorylation of dmIR in 293FT cells expressing dmIR wild-type (WT) or the indicated mutants. Cells were treated with 100 nM DILP5 for 10 min. Mean ± sem. N = at least 3 independent experiments. Statistical significance was determined using 2-way ANOVA. P values vs DILP5-treated dmIR WT. Exact P values are shown in the figure panel. g Autophosphorylation of dmIR in 293FT cells expressing dmIR wild-type (WT) or the indicated mutants. Cells were treated with 100 nM DILP2 for 10 min. Mean ± sem. N = 3 independent experiments. Statistical significance was determined using 2-way ANOVA. P values vs DILP2-treated dmIR WT. Exact P values are shown in the figure panel. Source data are provided as a Source data file.