A model for human FXII. (A) Schematic diagram of human FXII showing the positions of the heavy chain N-terminal peptide (N-term, orange-red), fibronectin type 2 (FN2, purple), epidermal growth factor 1 (EGF1, brown), fibronectin type 1 (FN1, magenta), EGF2 (dark gray), and kringle (KNG, light green) domains, the proline-rich region (PRR, dark green), the activation loop (light gray) and the catalytic domain (CD, yellow). The position of an anion-binding site (ABS) between FN2 and EGF1 is indicated in light blue, the activation cleavage site at Arg³⁵³ is indicated by a blue arrow, and the active site serine residue (Ser⁵⁴⁴) is indicated by the black bar. (B) AF-adjusted prediction (supplemental Figure 3C) for full-length human FXII shown as molecular surface representations. The 2 images shown are rotated 180° relative to each other. The color scheme is identical to that in panel A. Positions for the cleavage sites at Arg³⁴³ and Arg³⁵³ are indicated in dark blue. Most of the activation loop (Cys³⁴⁰-Arg³⁵³) is buried between the KNG and CD. (C) Predicted intramolecular interactions between the FXII FN2 domain (purple), KNG domain (light green), activation loop (light gray), and CD (yellow) are shown as cartoon and stick diagrams. Important basic amino acids are shown in dark blue, acidic amino acids in red, and tryptophan residues in olive. Positions of Arg³⁴³ and Arg³⁵³ are indicated in dark blue on the peptide backbone of the activation loop. The positions of Leu²⁶⁶ and Val³⁵⁹ on the peptide backbone are indicated. Hydrogen bonds are shown as dashed light blue lines, and cation-π interactions as dashed orange lines.