Fig. 6: Natural product theaflavine-3, 3′-digallate (TFBG) blocks the SHCBP1–PLK1 interaction. | Nature Communications

Fig. 6: Natural product theaflavine-3, 3′-digallate (TFBG) blocks the SHCBP1–PLK1 interaction.

From: Hyperactivation of HER2-SHCBP1-PLK1 axis promotes tumor cell mitosis and impairs trastuzumab sensitivity to gastric cancer

Fig. 6

a Interactions between PLK1 and different SHCBP1 deletion mutants analyzed by co-immunoprecipitation assays. WT wild type, IP immunoprecipitation, WCL whole cell lysates. b Interactions between SHCBP1 and the kinase domain (KD) or polo-box domain (PBD) of PLK1 analyzed by co-immunoprecipitation assays. c The bound conformation of the SHCBP1 355–562 aa and PLK1 PBD as predicted by the ZDOCK algorithm. The PBD is displayed in gray, and the SHCBP1 355–562 aa domain is displayed in red. d The protein complex of PBD and SHCBP1 355–562 aa displayed in ribbon mode from the same angle view as in c. The PBD residue bonds on the binding surface are marked in blue. e Interactions between SHCBP1 and different PLK1 deletion mutants containing residues on the binding surface of the mode analyzed by co-immunoprecipitation assays. f Interactions between SHCBP1 and different PLK1 mutants of four core amino acids on the binding surface of the mode analyzed by co-immunoprecipitation assays. g Computational model and interactions of TFBG and the SHCBP1–PLK1 complex (top left and right). Overall structure of the complex showing the binding of TFBG to PLK1 and SHCBP1, which are in green, gray, and red (bottom left and right). Architecture of PLK1 and TFBG showing interacting amino acids of PLK1 (gray) and TFBG (green). h Kinetic constant (Kd) analyses of TFBG interacting with PLK1 using surface plasmon resonance (SPR) assays. i, j Fluorescence resonance energy transfer (FRET) analysis of eCFP-PLK1 and eYFP-SHCBP1 in cells treated with TFBG at the indicated concentrations (i, n = 104 independent cells per group) and time (j, n = 100 independent cells per group). Data are the mean ± s.e.m. The p values were determined by one-way ANOVA and repeated measures one-way ANOVA. k TFBG dose-dependent response in SNU-216 cells for 4 days. Data are the mean ± s.e.m (n = 6 independent biological samples). Data of a, b, e, and f are representative of two independent experiments.

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