Deuterium uptake plots of HDX-MS of FIXa–FVIIIa complex. Changes in deuterium uptake in HDX-MS of FIXa–FVIIIa complex are displayed dark red (predominant change), yellow (moderate change), and gray on the crystal structure of FIXa, Protein Data Base (PDB) code 2wpm.¹⁴  Data indicate that major part of the protease domain and EGF-2 is affected by FVIIIa. Examples of deuterium uptake plots are also shown. Chymotrypsin numbering is indicated between brackets at the side of the peptide sequence. The red curves indicate FIXa in the absence of FVIIIa. FIXa incubated in the presence of FVIIIa is shown in pink. The complete set of peptides is reported in supplemental Figure 1.