Figure 2
Crystal structure of 4C2 in complex with MERS-RBD. (A) A cartoon representation of the structure. For clarity, the core and external subdomains of MERS-RBD are marked with a dashed line and the CDR loops of the heavy (HCDR1-3) and light (LCDR1-3) chains are highlighted in distinct colors and labeled. The η3 310 helix and the β8 strand in MERS-RBD that are referred to in the text are highlighted in salmon. The steric whereabouts of the hCD26 receptor based on the previous report7 was marked with the dashed arrow. (B) Structural basis of the neutralization by 4C2. Left panel: superimposition of the structure between 4C2 (gray) and MERS-RBD (green) with a previously reported structure of hCD26 (cyan) bound to MERS-RBD (magenta; PDB code: 4KR0). Upper right panel: steric hindrance created by CDR2 of 4C2 heavy chain with N229-linked carbohydrates (cyan sticks) of hCD26 and by the D/E loop of 4C2 heavy chain V-domain with the β1-strand-preceding loop of the receptor propeller IV. Lower right panel: footprint overlapping in MERS-RBD (shown in surface) between 4C2 and hCD26. Residues recognized by 4C2 and hCD26 are colored gray and cyan, respectively. The overlapped interface residues are highlighted in red and labeled. (C) A schematic diagram depicting the neutralization mechanism of 4C2 which blocks receptor binding by both steric hindrance and interface residue competition.
