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[Preprint]. 2025 Oct 1:2025.07.02.662799. Originally published 2025 Jul 4. [Version 3] doi: 10.1101/2025.07.02.662799

Figure 1. Auto-inhibited and open conformations of SHP2.

Figure 1.

(A) Crystal structure of SHP2WT in an auto-inhibited conformation, maintained by auto-inhibitory interactions between the N-SH2 (yellow) and PTP domain (green) (PDB code 4DGP). (B) Crystal structure of SHP2E76K in an open conformation. SH2 domains are rotated and N-SH2 domain is in a dramatically different position relative to the PTP domain (PDB code 6CRF). (C) AlphaFold2 model of SHP2 in an open conformation in which the N-SH2 domain adopts a distinct position and orientation relative to PDB structure 6CRF. (D) Crystal structure of SHP1C453S in an open conformation that largely resembles the AlphaFold2 SHP2 state (PDB code 3PS5). (E) Glu139 in the auto-inhibited state does not make any interdomain contacts (PDB code 2SHP). (F) Asp139 in auto-inhibited state does not make any interdomain contacts (PDB code 4NWG). (G) Glu139 interacts with Arg5 in the AlphaFold2 model of SHP2. (H) Glu137 interacts with Arg7 in the open state structure of SHP1 (PDB code 3PS5).