Fig. 2: Interactions forming the IL-11 signalling complex.
Bound IL-11 is depicted in green, IL-11Rα in purple, and gp130 in salmon. A Structure of the IL-11Δ10/IL-11RαD1-D3/gp130D1-D3 complex, with the five binding sites indicated. B Binding surfaces on (i) IL-11, (ii) IL-11Rα, and (iii) gp130. C Rearrangement of the AB loop on complex formation. Uncomplexed IL-11 is depicted in blue. (i) overlay of the crystal structure of IL-11Δ1049 (PDB ID: 6O4O) with the structure of the complex, showing the AB loop (F43-G65) rearrangement on complex formation. (ii) interactions within the AB loop, and between the AB loop and the α-helical core in the unbound state. (iii) and (iv) the AB loop rearrangement on complex formation. D Details of site-I contacts (IL-11, green; IL-11Rα, purple; gp130 salmon). (i) R169 of IL-11 protrudes into a pocket formed by several hydrophobic residues on IL-11Rα, (ii) contacts between the N-terminal end of the AB loop of IL-11 and IL-11Rα. E Details of site-IIA contacts, (i) contacts between C-helix arginine residues of IL-11 and gp130, (ii) contacts between the N-terminal end of the A helix of IL-11 and gp130. F Details of site-IIB contacts. G Details of site-IIIA contacts. (i) contacts between W147 and the N-terminal end of the AB loop of IL-11 with D1 of gp130. (ii) contacts between W147 and neighbouring residues of IL-11 with D1 of gp130. H Details of site-IIIB contacts. Cryo-EM density maps are contoured at 7 σ. I Representative ITC data for (i) the interaction between the IL-11Δ10/IL-11RαD1-D3 binary complex and gp130D2-D3; (ii) the interaction between the IL-11Δ10/IL-11RαD1-D3 binary complex and gp130D1-D3; and (iii), the interaction between the IL-11Δ10/IL-11RαD1-D3 binary complex and gp130EC. Representative of n = 3 independent experiments. For complete thermodynamic parameters, see Supplementary Table 4.
