FIGURE 3.

Structure of the ALK1^ECD-BMP9-ActRIIB^ECD ternary complex. A, the ternary complex comprised of one BMP9 homodimer (red/blue), two ALK1^ECD receptors (gold), and two ActRIIB^ECD receptors (green). The complex is shown as viewed from above (left) and from the side with the membrane below (right). B, superposition with the BMP2-ALK3^ECD-ActRIIB^ECD ternary complex (shown in ribbon) via the ligands reveals differences in receptor positioning (BMP2 homodimer colored pink/light blue; ALK3^ECD and ActRIIB^ECD receptors colored light gray and dark gray, respectively; ALK1^ECD-BMP9-ActRIIB^ECD complex colored as in panel A). C, superposition of ALK1^ECD and ALK3^ECD at the BMP9 interface (shown in surface representation) reveals a 20° rotation of the ALK1 protomer pivoted around helix α1. D, close-up view of helix α1, F1, F2, and F3 loops from ALK^ECD and ALK3^ECD (shown as schematic). Repositioning of these elements in ALK1 results in a novel set of receptor-ligand interactions.