Fig. 5: Structural model of TCPTP autoinhibition. | Nature Communications

Fig. 5: Structural model of TCPTP autoinhibition.

From: The catalytic activity of TCPTP is auto-regulated by its intrinsically disordered tail and activated by Integrin alpha-1

Fig. 5

a Bar graph reporting changes in TCPTP catalytic activity due to mutations in the catalytic domain (TCPTPL1) and the C-terminal tail (TCPTPC-term) using pEGFR peptide-1 as a substrate derived from the EGFR cytoplasmic tail. Data are presented as the mean of nine independent reactions (n = 9; mean ± standard deviation, SD). *** indicates p-value of <0.001 (p = 0.0009) and **** indicates p-value of <0.0001, obtained from one-way ANOVA analysis with Tukey’s multiple comparison test. b Model of TCPTP autoinhibition that integrates the NMR, CX-MS and activity data. Residues ~300–340 from the TCPTP C-terminal tail adopt an ensemble of conformations (depicted in different colors: cyan, navy, magenta, red, and yellow), akin to a windshield wiper, to dynamically block substrate access to the TCPTP active site (yellow). Residues with CSPs are colored as in Fig. 3e and show how residues 344–385 bind the backside of TCPTP. Source data are provided as a Source Data file.

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