Sulfated-Y1680 in the FVIII-a3 acidic peptide and R816 in the basic groove of VWF-D′ directly interact. (A) FVIII-a3, shown in yellow with acidic residues labeled, sits in a basic groove of VWF-D′ formed by a network of arginine residues. VWF-D′ is rendered in surface view colored by domain identity (left) or electrostatic potential (right) (acidic: red, basic: blue, neutral: white) using the APBS plugin in PyMol. Scale is –5 to +5 kT/e. (B) Details of FVIII-a3/VWF-D′ interface. FVIII-a3 peptide in yellow, VWF-D′ in red, FVIII-C1 in cyan, and FVIII-A3 in blue. Direct polar interactions are indicated by dotted lines, with interacting residues labeled. Residues with known mutations that cause bleeding disorders are labeled in red.