Biophysical and structural insight into the USP8/14-3-3 interaction.
The ubiquitin-specific protease 8 (USP8)/14-3-3 protein-protein interaction has recently been shown to exert a significant role in the pathogenesis of Cushing's disease (CD). USP8 is a deubiquitinase that prevents epidermal growth factor receptor (EGFR) degradation. Impairment of 14-3-3 binding leads to a higher deubiquitination of EGFR and results in a ... higher EGFR signaling and an increased production of adrenocorticotropic hormone. Here we report the high-resolution crystal structure of the 14-3-3 binding motif of USP8 surrounding Ser718 in complex with 14-3-3ζ and characterize the interaction with fluorescence polarization and isothermal titration calorimetry. Furthermore, we analyze the effect of USP8 mutations identified in CD on binding to 14-3-3.
Mesh Terms:
14-3-3 Proteins, Crystallography, X-Ray, Endopeptidases, Endosomal Sorting Complexes Required for Transport, ErbB Receptors, Humans, Pituitary ACTH Hypersecretion, Protein Structure, Quaternary, Proteolysis, Ubiquitin Thiolesterase
14-3-3 Proteins, Crystallography, X-Ray, Endopeptidases, Endosomal Sorting Complexes Required for Transport, ErbB Receptors, Humans, Pituitary ACTH Hypersecretion, Protein Structure, Quaternary, Proteolysis, Ubiquitin Thiolesterase
FEBS Lett.
Date: Dec. 01, 2017
PubMed ID: 29473952
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