Figure 6: Mapping of GM-CSF and IL-2 binding footprints.
From: Structural basis of GM-CSF and IL-2 sequestration by the viral decoy receptor GIF
(a) The GM-CSF and IL-2 interaction epitopes on GIF are mutually exclusive. Schematic overview of the effect of GM-CSF interface residue mutations on GIF. GIF is shown in dark green, and the GM-CSF and putative IL-2 binding sites are shown as outlines in blue and orange respectively. Mutated GIF residues (R45A, R106A, R188A, K211A and H232A) are coloured in different tints of red, depending on the resulting reduction in affinity for GM-CSF (120-fold affinity reduction: bright red, 10 fold affinity reduction: light pink). See also Supplementary Fig. 5 and Supplementary Table 5. (b) GIF serves as a competitive viral decoy receptor against the GM-CSF receptor. Alignment of the GIF:GM-CSF crystal structure (GIF: green, ovine GM-CSF: blue) with human GM-CSF (yellow) in the GM-CSF:GM-CSFR complex32 (PDB code: 3CXE, GMR α: brown, GMR cβ; grey). GM-CSF binding on GIF through α-helices αA and αD fully overlaps with GM-CSF binding epitopes on GM-CSFR α and cβ. Insets show a detailed zoom of binding interfaces to human and ovine GM-CSF helix αA (inset 1) and αD (inset 2). Residues on GIF or GM-CSFR involved in ovine/human GM-CSF binding are labeled and shown as sticks, polar interactions are shown as dashed lines.
