Fig. 1: Crystal structures and SAXS curves from closed SHP2 and open SHP2^E76K.

a Crystal structure of autoinhibited wild-type SHP2 (SHP2^wt). In the autoinhibited state (PDB ID 4DGP¹⁵), SHP2^wt adopts a closed conformation; the N-SH2 domain (cyan cartoon) blocks the catalytic site (red) of the PTP domain (pink) with the blocking loop (blue). The N-SH2 domain is connected to PTP in tandem with the homologous C-SH2 domain (orange). b Crystal structure of the constitutively active SHP2^E76K mutant. In the active state, SHP2^E76K adopts an open conformation with the catalytic pocket exposed to the solvent. The crystal structure of SHP2^E76K (PDB ID 6CRF⁴⁴) reveals a 120° rotation of the C-SH2 domain and the relocation of the N-SH2 domain to a PTP surface opposite the catalytic site. c Small-angle X-ray scattering (SAXS) curve calculated from the solution ensemble of the autoinhibited wild-type SHP2 (unrestrained MD simulation from PDB ID 4DGP¹⁵, red line) is compared with the experimental curve (black dots)⁴⁶, reported as raw data, and with the single-structure model fitting by Pádua et al. (green line)⁴⁶. d The SAXS curve calculated from the crystal structure of the constitutively active SHP2^E76K mutant (restrained MD simulation from PDB ID 6CRF⁴⁴, red line) is compared with the experimental curve (black dots)⁴⁶, reported as raw data, and with the single-structure model fitting by Pádua et al. (green line)⁴⁶, Experimental, model-estimated, and calculated radii of gyration (R_g) are reported in each panel in black, green, and red font, respectively.