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[Preprint]. 2023 Jul 30:2023.07.10.548257. Originally published 2023 Jul 10. [Version 2] doi: 10.1101/2023.07.10.548257

Figure 1. Structure and regulation of SHP2.

Figure 1.

(A) Domain architecture diagram of SHP2. Relevant mutations and the catalytic cysteine (C459) are indicated. (B) SHP2 is kept in its auto-inhibited state by interactions between the N-SH2 and PTP domain (PDB: 4DGP). In its active state, the catalytic cysteine is accessible. The structure of SHP2E76K (PDB: 6CRF) is used to represent the active state. (C) The SH2 domains of SHP2 bind to tyrosine-phosphorylated upstream proteins, such as transmembrane receptors, inducing a conformational change that activates SHP2. (D) Disease-associated mutations cluster largely, but not exclusively, on the interdomain interface between the N-SH2 and the PTP domain (PDB: 4DGP). (E) Mutations in or near the N-SH2 binding pocket (PDB: 6ROY). (F) Mutations in or near the C-SH2 binding pocket (PDB: 6R5G).