Fig. 5: Domains of the M region form a scaffold for the structure and lie in a plane with a dihedral angle of ~60° relative to the plane of the SCR domains.

a Cartoon representation of the isolated M domains of the 2:2 PAPP-A·STC2 complex. The positions of the domains (M1 through M6) are indicated, and domain boundaries are shown by alternating shades of cyan. b Cartoon representation of the CD (red, active site cleft facing left) and domains M1-4 (cyan), showing the positions of inter-strand loops of M2 relative to the active site cleft within the PAPP-A·STC2 complex. c Cartoon representation showing the M1 and M2 domains, one STC2 subunit, and the disulfide bond between C732 of M2 and C120 of STC2, which is responsible for covalent linkage between PAPP-A and STC2. Inset shows map around the C120-C732 disulfide bond. The map (MAP1) was contoured at 2.0 σ. d Assessment of the ability of wild-type PAPP-A and PAPP-A(C732) to form a covalent complex with STC2. After incubation (16 h), the separately synthesized proteins were subjected to non-reducing SDS-PAGE and visualized by Western blotting for PAPP-A. The PAPP-A(C732) variant is unable to form the covalent PAPP-A·STC2 complex with STC2. The experiment was repeated three times with similar results. Source data are provided as a Source data file. e Cartoon representation of the PAPP-A dimerization region within the PAPP-A·STC2 complex, showing domains M5-6 and SCR1 with the two PAPP-A subunits colored differently (cyan and transparent blue). The enlarged view emphasizes the dimerization interface and the disulfide bond between the two PAPP-A subunits. Note that the left M5-6 domains continue in the right SCR1 domain and vice versa. f Cartoon representation of the 10 SCR domains (shades of blue) of the PAPP-A·STC2 complex shown in two orientations (SCR1 (C1215-V1283), SCR2 (D1284-L1344), SCR3 (M1345-V1413), SCR4 (T1414-M1474), and SCR5 (Q1475-C1554)). g Top view of the PAPP-A·STC2 complex with only the M domains (cyan) and the SCR domains (blue) shown to emphasize their relative orientation. The lines drawn indicate the approximate planes in which M1-4 and the SCR domains, respectively, lie. The dihedral angle between the planes is indicated.