Structure of FV short. The structure, shown in front (A) and side (B) views, includes all residues of the native FV short protein (except 1 B domain residue encoded by the codon that spans the FV short splicing junction). The A1 (wheat), A2 (pale green), and A3 (pale yellow) domains are arranged in a triangular fashion on top of the phospholipid binding C1 (light pink) and C2 (pale cyan) domains. The B domain (light blue) spans from R709 to R1545 and wraps around the A domains. The thrombin-cleavage sites at R709 and R1545, as well as the partially exposed APC-cleavage sites at R306 and R506, are shown. The “gate” and “lid” regions of the A2 domain are highlighted in blue and orange, respectively. The exposed acidic segment of the A2 domain and the portions of the B (and A3) domains contributing to the negatively charged surface that may serve as binding site for the protease domain of FXa and the basic region of TFPIα are encircled in red. The approximate locations of the 4 hydrophobic clusters (HCs) surrounding the acidic cluster (AC) are marked in white. HC2 contains the PLVIVG hydrophobic patch required for synergy with PS in the TFPIα-mediated inhibition of FXa. Adapted from Figure 2 in the article by Mohammed et al that begins on page 3215.