Structural basis of G6b-B recognition by SHP2. The specific interactions are shown by comparison of N-SH2 apo (black) and N-SH2 + 1 equivalent p-ITIM (sky blue) (A), C-SH2 apo (black) and C-SH2 + 1 equivalent p-ITSM (red) (B), and tandem SH2 apo (teal) and tandem SH2 + 1 equivalent p-ITIM+p-ITSM (red) (C). Selected chemical shift perturbations in SOFAST-HMQC NMR spectra are labeled. (D) Lowest-energy model of tandem SH2 bound to p-ITIM+p-ITSM generated by HADDOCK based on restraints generated from the NMR data. Residues showing large chemical shift perturbations are shown in blue and are defined as active residues directly involved in interaction with the peptide. Residues showing small, yet significant, chemical shift perturbations are shown in cyan and are defined as passively involved residues.