Schematic representation of fV and fV short. (A) A1-A2-B-A3-C1-C2 domain organization of fV (2196 residues total) and details of the B domain containing the BR (963KPGKQSGHPKFPRVRHKSLQVRQDGGKSRLKKSQFLIKTRKKKKEK1008) and AR (1493DYIEIIPKEEVQSSEDDYAEIDYVPYDDPYKTDVRTNINSSRDPD1537) that interact to keep fV in its inactive state.1,5-9 The hydrophobic patch 1481PLVIVG1486 is highlighted preceding the AR. The sites of thrombin activation (R709, R1018, R1545) and APC inactivation (R306, R506) are indicated. (B) A1-A2-B-A3-C1-C2 domain organization of the splice variant fV short carrying a deletion of 703 residues, from 756 through 1458, in the B domain (1493 residues total). The deletion removes the site of thrombin activation at R1018 and the entire BR, which unmasks the hydrophobic patch 1481PLVIVG1486 and the AR region to promote TFPIα binding. The cryo-EM structure of fV short (Figure 2; supplemental Figure 3) reveals all residues of the A1-A2-A3-C1-C2 assembly. Reproduced with modifications,10 copyright Elsevier (2022).
