Components of the EC on the membrane surface before ternary complex formation. (A) Domain compositions of each EC component protein modeled in this study, with the sequence coverage of the template structures mapped below each protein. Residues are numbered based on the mature protein sequence (ie, the secreted or cell-surface form) in black below each component, whereas the corresponding residue numbers of the protein precursors are listed in gray for reference. The SPDs in the template crystal structures were reported following the chymotrypsinogen numbering system³ (gray italicized numbers above SPDs). (B) The membrane-bound sTF:FVIIa complex (blue and orange, respectively) next to membrane-bound FX (purple). FVIIa and TF first form a binary complex, which greatly increases the enzymatic activity of FVIIa, after which FX is recognized as a substrate. Assembly of the EC and the rate of FX activation are also enhanced significantly by association with anionic phospholipids in the membrane. Details of building the sTF:FVIIa and FX models are given in the supplemental Data. Bound Ca²⁺ ions are shown in green. (C) Closeup on the TF exosite and adjacent FVIIa-GLA domain. TF exosite residues (Y157, K159, S163, G164, K165, K166, and Y185)⁴ are highlighted, as is residue R36 of the nearby FVIIa-GLA domain,⁵ all of which are implicated from mutagenesis studies as potential binding partners for the FX-GLA domain. The black line depicts the approximate upper boundary of the membrane surface, as seen in MD simulations of the sTF:FVIIa complex.⁶ AP, activation peptide; CT, cytoplasmic domain; FIB, fibronectin type 3 domain; SP, signal peptide; TM, transmembrane.