Human fXI. This schematic diagram shows the primary amino acid sequence, general domain structure, and the disulfide bonds (cysteine residues shown as the letter C in black circles) for a human fXI subunit. Each subunit is comprised of 4 apple domains (A1 through A4) and a C-terminal trypsin-like catalytic domain. The mature molecule in plasma is a dimer of 2 of these subunits connected through a hydrophobic interface on the A4 domains, with the cysteines at position 321 in each subunit forming an interchain-disulfide bond. Conversion of fXI to fXIa involves proteolytic cleavage of the bond after arginine 369 (R369, indicated by the black arrow). This cleavage can be produced by fXIIa or thrombin. Amino acids thought to be required for fIX binding to the fXIa A3 domain are indicated in red and residues that comprise the heparin binding site on the catalytic domain are shown in blue. The position of the active site serine residue (S557) is indicated in yellow. (Used with permission from McMullen et al.⁵⁹ )