Fig. 5: Molecular dynamics simulation of the carboxyl terminus of MAS bound with MAGI3 to block the coupling of G protein with the intracellular loop 2 (ICL2) of MAS. | Cell Death & Disease

Fig. 5: Molecular dynamics simulation of the carboxyl terminus of MAS bound with MAGI3 to block the coupling of G protein with the intracellular loop 2 (ICL2) of MAS.

From: MAGI3 enhances sensitivity to sunitinib in renal cell carcinoma by suppressing the MAS/ERK axis and serves as a prognostic marker

Fig. 5: Molecular dynamics simulation of the carboxyl terminus of MAS bound with MAGI3 to block the coupling of G protein with the intracellular loop 2 (ICL2) of MAS.

A Predicted AlphaFold models of MAGI3-PDZ1, with the carboxylate binding loop (Gly-419, Phe-420, Gly-421, Phe-422, Thr-423, Ile-424) highlighted in blue, and other residues in green. MAS-PBM is colored in oranges (Cys-316, Asn-317, Thr-318, Val-319, Thr-320, Val-321) and magentas (Glu-322, Thr-323, Val-324, Val-325). B, C Molecular simulation of MAGI3-PDZ1/MAS-PBM complex. Front (B) and side (C) views of the interaction between MAGI3-PDZ1/MAS-PBM. D. Ribbon diagram representation of MAGI3-PDZ1 and MAS-PBM structure. Colors correspond to those in Fig. 5A. The “ETVV” motif of MAS is labeled. E Stereoview of the detailed interface of MAGI3-PDZ1/MAS-PBM complex. Dotted lines represent chemical bonds. Right panels show magnifications of the wireframe areas on the left. The “GFGFTI” motif of MAGI3-PDZ1 and “ETVV” motif of MAS are labeled. F Crystal structure of MRGPRX2-Gq signaling complex (PDB: 7S8N). The ICL2 that interacts with Gαq protein on MRGPRX2 is colored in pink. G Structural comparison of MAS AlphaFold model with MRGPRX2. Lower panel show magnifications of the wireframe area on the upper. H Molecular dynamics simulation of MAS/MAGI3-PDZ1 complex, indicating the interaction of MAGI3-PDZ1 with MAS-PBM obscuring the ICL2 on MAS that interacts with G protein.

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