Fig. 6: EatA-MUC2 docking model.

EatA is shown in green, MUC2 chain A in blue and MUC2 chain B in cyan. A Schematic overview of an oligomeric MUC2 filament drawn to scale. The N- and C- termini where the disulfide-mediated oligomerization occurs are annotated. The predicted complex between the dimeric MUC2 C-terminal region and EatA is shown as an inset. B EatA-MUC2 docking model after 50 ns molecular dynamics (MD) simulation, surface (excluding glycans) and cartoon. Chains A and B of the MUC2 homodimer are labeled A and B, glycans on chain A are shown in magenta and those on chain B in orange. In the central figure cartoon representation, the different protein domains are shown in different colors: EatA Protease domain in magenta, Passenger domain in green and DUF in black; and MUC2 VWCN in blue, VWD4 in cyan, C8_4 in green, TIL4 in orange and VWC1 in red. The complex is turned clockwise by 90˚ on the y-axis in the bottom figure and 180˚ in the upper one. Both are reduced by 50% in size with respect to the central figure. C MUC2-IgA1 (PDB: 1IGA) superposition. IgA chain A and C surface is shown in light orange, and chain B and D in pink. MUC2 is represented by cartoons and sticks. IgA1 and MUC2 N- and C- termini are labeled, and IgA domains are specified. The IgA region predicted to interact with IgAP is marked with a red star. D EatA active site with human or E mouse MUC2 PTS3 detailed interaction before (0 ns) and after (50 ns human PTS3 and 10 ns for mouse PTS3) MD simulation. O-glycans are shown in orange, and the PTS3 main chain in cyan. Only the surface representation of EatA is shown. For human PTS3, the lysine in the P1’ positions is labeled and marked in pink. In mouse PTS, all lysines (pink) and Q3794 (green) are marked. The S1 and S2’ pockets are annotated, D120 in S2’ is colored in red, and the catalytic serine (S267) in yellow.