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. 2015 Nov;6(11):849-52.
doi: 10.1007/s13238-015-0192-y.

Molecular mechanism for the substrate recognition of USP7

Jingdong Cheng  1   2 , Ze Li  1   2 , Rui Gong  1 , Jian Fang  1 , Yi Yang  1 , Chang Sun  1 , Huirong Yang  1 , Yanhui Xu  3   4   5
Affiliations

Molecular mechanism for the substrate recognition of USP7

Jingdong Cheng et al. Protein Cell. 2015 Nov.
No abstract available

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Figures

Figure 1
Figure 1
Crystal structure of the USP7-ICP0 complex. (A) Color-coded domain architecture of human USP7 (top) and ribbon representations of the overall structure of the TUDUSP7-ICP0 complex (bottom). The color scheme is used in all structural figures. The ICP0 peptide is colored in forest. The N- and C-termini of USP7 and ICP0 are indicated. (B) Closed-up view of the intermolecular interaction. USP7 and ICP0 are shown in ribbon representations. Critical residues for the interaction are shown in stick representation. Hydrogen bonds are shown as dashed lines. (C) GST pull-down assay for the interaction between TUDUSP7 and ICP0. Wild type and mutants of GST-tagged ICP0 (613–633) were incubated with TUDUSP7 and immobilized on glutathione resin. The bound proteins were subjected to SDS-PAGE and visualized by Coomassie blue staining. The free GST is resulted from protein purification and would not affect the results. (D) Comparison of TUDUSP7-ICP0 and USP7-DNMT1 structures. In USP7-DNMT1 structure, USP7 is colored in lemon and the KG-Linker in yellow. Critical residues for the interactions are shown in stick representation. Hydrogen bonds are shown as dashed lines
Figure 2
Figure 2
TUD is a new substrate-binding domain. (A) DNMT1, UHRF1, ICP0, histone H3 and H2A bind to the same acidic pocket of TUDUSP7. The GST pull down assay were performed as in Fig. 1C. (B) The alignment of the corresponding sequences of DNMT1, UHRF1, ICP0, H3, and H2A. Identical and highly conserved residues are highlighted in dark green and conserved residues in light green. This indicated that all these protein have the conserved KxxxK motif. (C) ITC measurement of the interactions between TUDUSP7 and various peptides. (D) The interactions between full-length USP7 and its binding proteins. HEK293T cells were transiently co-transfected with FLAG-tagged proteins and GFP-tagged USP7 (wild-type and mutants) followed by immunoprecipitation. The proteins were detected by immunoblotting using the indicated antibodies
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