A model for the activation of FXI and factor IX on activated platelets.
The FXI or FXIa molecule is a dimer composed of 2 identical 80-kd polypeptides, each containing 4 apple domains (designated A1 through A4), and one trypsin-like catalytic domain. For the sake of clarity, schematic representations of FXI are shown only with apple domains involved in the relevant interaction. FXI binds to the surface of an activated platelet through one of its A3 domains in a reaction that requires either HK and Zn2+, or prothrombin (PT) and Ca++. HK or PT (shown interacting with the A1 domain of FXI in the solution phase of the diagram) appears to be required for FXI to be in the proper conformation for binding to the platelet but does not appear to be a necessary component of a platelet-binding site for FXI. It is not known if FXI interacts with either HK or PT on the platelet surface. Furthermore, it is not clear if HK and PT interact with one or both polypeptides of the FXI dimer. FXI bound to the platelet is activated to FXIa by thrombin, factor XIIa, or factor XIa.13,14 Factor IX binds to FXIa through the heavy chain not involved in binding to the platelet. Available data suggest that the factor IX binding site on FXIa involves components of the A2 and A3 domains.23,24,27 FXIa then converts factor IX (FIX) to factor IXa (FIXa) in a reaction requiring calcium ions.6Abbreviations: FXI, factor XI; FXIa, factor XIa; FIX, factor IX; FIXa, factor IXaβ; A1 through A4, factor XI apple domains 1 through 4, respectively; HK, high molecular weight kininogen; PT, prothrombin.
