Structural interpretation of type 2N VWD mutations. (A) Ribbon diagram showing the position of the reported TIL′E′ type 2N missense mutations. Noncysteine mutations are shown with green spheres, and those involving cysteine residues are colored black. The TIL′ domain is colored blue, and the E′ domain colored red. A wall-eye stereo view is shown in supplemental Figure 12. (B) Surface representation of TIL′E′ with the type 2N noncysteine mutations colored green, and those involving cysteine residues colored black. The surface of the TIL′ domain is shown with a light-blue color, and the surface of the E′ domain is shown with a light-red color. (C) Electrostatic surface potential of TIL′E′, with blue (red) indicating positive (negative) charge. The view on the left side shows the region of concentrated positive charge density, circumscribed by a yellow dashed line, which is the putative binding site for the a3 domain of the FVIII light chain. The views on the right side of all panels are a 180° rotation of the views shown on the left.