Site‐specific functional roles of the Factor X activation peptide in the intrinsic tenase‐mediated Factor X activation. Issue 12 (28th February 2022)

• Record Type: Journal Article
• Authors: Carnbring Bonde, Amalie; Rosenørn Hansen, Sofie; Johansson, Eva; Rose Bjelke, Jais; Lund, Jacob
• Is Part Of: FEBS letters. Volume 596:Issue 12(2022)
• Page Start: 1567
• Page End: 1575
• Publication Date: 2022-02-28
• Subjects: activation peptide -- enzyme kinetics -- Factor X -- intrinsic tenase -- site‐directed mutagenesis; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1002/1873-3468.14321
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : 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. Abstract : The coagulation protease Factor X normally circulates in blood as an inactive zymogen precursor. The conversion of Factor X into an active protease requires the proteolytical removal of a flexible peptide sequence. Using site‐directed mutagenesis, we show that that this peptide sequence plays a critical role in both promoting and protecting Factor X activation.