Structural and functional paratopes of CB3s for hBR3 and mBR3 binding. (A) The CB3s CDR binding surface of heavy (gray) and light (white) chains with structural contacts colored according to the extent buried by BR3. Residues are labeled using the same format as in Figure 4. (B) Residues that contribute energetically to binding hBR3 or (C) mBR3 are mapped on the structure of CB3s with color coding according to their importance as indicated by shotgun alanine–scanning F values. In panel C, side chains for hBR3 residues that differ in mBR3 are shown and labeled (white) with the human-to-murine substitution. The functionally important disulfide in CDR-H3 is colored magenta. The dotted line depicts the perimeter of the main structural paratope.