Figure 1

Crystal structures of inhibitory VHHs in complex with the major adhesive subunit FaeG. (A) From left to right, molecular surface representation of the structure of FaeG_ad in complex with lactose (stick representation), co-complex structure of V1 with FaeG_ac, co-complex structure of V2 with FaeG_ac and finally the co-complex structure between V3 and FaeG_ad. The orientation of FaeG in each panel is identical, the additional binding domain grafted onto the FaeG immunoglobulin-like core is colored red and the VHH in the last three panels is colored in blue. Variation between the different FaeG variants is colored on the molecular surface of FaeG_ad in green. The lactose binding site on the surface of FaeG_ad is indicated by a yellow circle for clarity. (B) Comparison of the binding conformation of V1 (yellow) and V2 (blue). The different CDR regions of the VHHs are indicated and colored in orange (V1) and purple (V2). In V2 the CDR2 is shifted upwards and located at a further distance from the FaeG surface, whereas the conformation of the CDR3 is near identically traced. (C) Close-up on the interactions formed in the complex between V3 and FaeG_ad. (D-G) Interactions formed between V1 and FaeG_ac (D,E) and V2 and FaeG_ac (F,G) in different orientations. In each panel FaeG is colored gray and the additional variable subdomain in cyan. VHHs are depicted in yellow and water molecules are represented as red spheres. Interacting residues of the VHH and FaeG adhesin are labeled respectively blue and black and shown as stick model with nitrogen atoms colored blue and oxygen atoms in red. Hydrogen bonds are depicted as orange dashed lines.