Fig 1: Structural analysis of the IL-23:MA12 complex.(a) Assembly of the IL-23–MA12 complex. (Left) the IL-23:MA12 complex with IL-23 in surface mode and the MA12 Alphabody in cartoon mode. (right) The complex is rotated by 180° and IL-23 is shown in cartoon mode and MA12 in surface mode. MA12 is coloured in pink, p19 in green and p40 in grey. The MA12-interacting surface of p19 (800 Å2) is indicated in dark green and the p19-interacting surface of MA12 (840 Å2) in magenta. The linker regions between helices A and B (L1) and B and C (L2) in MA12 are represented as dashed lines. (b) Top view of the IL-23–MA12 complex. MA12 interacts with helix D and the AB and BC loops of p19. (c) View of the isoleucine core of the Alphabody core in MA12 and engagement of the p19 subunit via the interhelical groove presented by helices A and C of MA12. (d) Detailed view of the IL-23:MA12 interactions around residue W156 in the p19 subunit of IL-23. (e) Detailed view of the interactions of MA12 helix C with p19. Residue numbering in the structure of human IL-23 reported herein reflects the sequence numbering of the protein in Uniprot. Thus, residue numbers in the p19 subunit of human IL-23 differ by 19 with respect to equivalent residues in PDB entries 3DUH, 3D85, 3D87, 3QWR and 4GRW (for example, W156 in the p19 subunit of human IL-23 is equivalent to W137 in previously reported structures). (f) Comparisons of sequences corresponding to helices A and C in the two best matured Alphabodies MA12 and MB23, against the reference sequences in matLib. Positions labelled with ‘x’ corresponding to variable amino-acid position. Amino acids in MA12 that are involved in binding to human IL-23 are shown in bold.