Site-specific functional roles of the Factor X activation peptide in the intrinsic tenase-mediated Factor X activation

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.

Automated summary

This study investigates the conversion of zymogen Factor X to an active protease and reveals the importance of proline residues in efficient proteolysis. It also identifies essential interaction sites for Factor IXa and the intrinsic tenase complex, as well as the role of a carbohydrate chain in activator specificity.