Electrostatics of the FVa-APC complex. Relevant domains and structural epitopes are labeled for FVa (A1, A2, A3, C1, and C2 domains; latch, sites of cleavage at R306 and R506) and APC (PD, EGF1, EGF2, and Gla domains; S1 site, 30-, 60-, 70-, and autolysis loop). (A) Surface representation of the cryo-EM structure of the FVa-APC complex (PDB 9MOV) oriented as in Figure 1A (left) or showing the back of FVa in the complex after counterclockwise 90° rotation (center). A further 90° counterclockwise rotation exposes the ⁶⁵⁴VKCIPDDDEDSYEIFEP⁶⁷⁰ segment or “latch” of the A2 domain positioned over the PD of APC (right). (B) Electrostatic potential surface maps calculated in UCSF ChimeraX according to the Coulomb law for the FVa-APC complex in the same orientation as panel A (left). The 2 proteins are pulled apart (middle) to reveal a small electropositive epitope of APC defining the surface of interaction with FVa that becomes more evident after 75° rotation of FVa and APC in opposite directions (right). The surface is defined by region around R506 of FVa docking into the S1 site of APC and the electronegative latch docking as an exosite ligand onto the electropositive 70-loop of the enzyme.