Extended Data Fig. 5: Experimentally observed flexibility in the IL-12 and IL-23 protein complexes.
From: Structures of complete extracellular receptor assemblies mediated by IL-12 and IL-23
a, Structural superposition of IL-12 (5 observations) using p40D2D3 as a reference showing inter domain flexibility. mIL-12Rβ1D1-D5 bound structures display a preferred orientation of the p40D1 especially with regards to the p40D1βA-βB and βE-βF loops which are part of the interface. The p35 subunit is also twisted away from p40 upon mIL-12Rβ2 binding. b, Structural superposition of mIL-12Rβ2 (2 structures) using p35 as a reference displays flexibility beyond the p35: mIL-12Rβ2D1 interface. c, structural superposition of hIL-23 (21 observations total) using the p19 helices as a reference showing inter domain flexibility. IL-23R bound structures display an α-helical to 310-helical switch at the N-terminal tip of the D-helix which is the interface hotspot. d, structural superposition of hIL-23 (21 observations of hIL-23 and 1 hp40 only) using the p40D2D3 as a reference showing inter domain flexibility. hIL-12Rβ1 bound structures display a preferred orientation of the p40D1 especially with regards to the p40D1βA-βB and βE-βF loops which are part of the interface. e,f, Structural superpositions of hIL-23R using hIL-23RD1 as reference (e) and human and mouse IL-12Rβ1 using IL-12Rβ1D1 as a reference (f) display flexibility in the receptor domains a well as in cytokine binding. Models utilized in figures are PDB IDs: 1f45, 3hmx, 3duh, 3d85, 3d87, 3qwr, 4grw, 5mj3, 5mj4, 5mxa, 5mzv, 5njd, 6uib, 6wdq, 6sff, 6smc, 6sp3, 7pur, 7r3n, 8odz, 8oe0, 8oe4, 8cr6, 8cr5, 8cr8, 8c7m, 8odx.
