6F09

Binary complex of 14-3-3 zeta with ubiquitin specific protease 8 (USP8) pSer718 peptide

Summary for 6F09

• Entry DOI: 10.2210/pdb6f09/pdb
• Descriptor: 14-3-3 protein zeta/delta, Ubiquitin carboxyl-terminal hydrolase 8 (3 entities in total)
• Functional Keywords: 14-3-3, usp8, phosphosite, binary complex protein-peptide, signaling protein
• Biological source: Homo sapiens (Human); More
• Cellular location: Cytoplasm : P63104 P40818
• Total number of polymer chains: 8
• Total formula weight: 111689.88

Authors

Centorrino, F.,Ballone, A.,Ottmann, C.,Guo, S.,Leysen, S. (deposition date: 2017-11-17, release date: 2018-03-07, Last modification date: 2024-10-16)

Primary citation

Centorrino, F.,Ballone, A.,Wolter, M.,Ottmann, C.
Biophysical and structural insight into the USP8/14-3-3 interaction.
FEBS Lett., 592:1211-1220, 2018

PubMed Abstract: 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.

PubMed: 29473952
DOI: 10.1002/1873-3468.13017

Experimental method

X-RAY DIFFRACTION (1.594 Å)