Schematic representation of the PS mutants used in the study. Human PS consists of an N-terminal Gla domain, followed by the TSR, 4 EGFs, and a large SHBG-like region. In each PS mutant, regions in black denote the prothrombin Gla domain. Gla_FII-ΔTSR-PS is a PS molecule whose TSR has been deleted (residues 46-74, PS numbering) and whose Gla domain (residues 1-45, PS numbering) has been replaced by the prothrombin Gla domain (residues 1-45, prothrombin numbering). In the Gla_FII-ΔTSR-PS chimera, the prothrombin Gla domain ends at Thr45, and the PS EGF1 domain starts at Ala75. Gla_FII-PS is a PS molecule in which the only change is the replacement of the PS Gla domain with the prothrombin Gla domain. In Gla_FII-PS, the prothrombin Gla domain ends at Thr45, and the PS TSR starts at Val46. In the PS mutant F1_FII-Gla_PS-PS, the amino acid residues 33, 35, 36, and 39 of PS Gla domain face 1 are replaced with the corresponding residues of prothrombin. In F1_FII-Gla_PS-PS, the amino acid residues 21, 23, 24, 28, 34, 41, and 45 of PS Gla domain face 2 are replaced with the corresponding residues of prothrombin. In F12_PS-Gla_FII-PS, the amino acids at position 21, 23, 24, 28, 33, 34, 35, 36, 39, 41, 42, and 45 in Gla_FII-PS are replaced with the corresponding residues of PS.