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Site‐specific functional roles of the Factor X activation peptide in the intrinsic tenase‐mediated Factor X activation
Author(s) -
Carnbring Bonde Amalie,
Rosenørn Hansen Sofie,
Johansson Eva,
Rose Bjelke Jais,
Lund Jacob
Publication year - 2022
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.14321
Subject(s) - zymogen , factor ixa , chemistry , factor x , active site , proteolysis , biochemistry , protease , enzyme activator , peptide , site directed mutagenesis , activator (genetics) , glycosylation , enzyme , biology , mutant , platelet , gene , immunology , thrombin
The conversion of zymogen Factor X (FX) to an active protease involves the removal of a 52‐residue long activation peptide (AP). Through site‐directed mutagenesis, we investigate the role of the AP and demonstrate that the high abundance of proline residues is important for efficient proteolysis of FX. Moreover, we identify an essential interaction site for Factor IXa (FIXa) between residues 22 and 30 (AP numbering) and find that the residues between 31 and 41 may provide an important interaction site for the intrinsic tenase complex, composed of Factor IXa (FIXa) and Factor VIIIa (FVIIIa). Finally, we suggest that the carbohydrate chain at Asn‐39 restricts the activator specificity, as elimination of this glycosylation site increases the activation rate for activation by FIXa and FXa.