Unknown

Dataset Information

0

A Supramolecular Stabilizer of the 14-3-3?/ER? Protein-Protein Interaction with a Synergistic Mode of Action.

ABSTRACT: We report on a stabilizer of the interaction between 14-3-3? and the Estrogen Receptor alpha (ER?). ER? is a driver in the majority of breast cancers and 14-3-3 proteins are negative regulators of this nuclear receptor, making the stabilization of this protein-protein interaction (PPI) an interesting strategy. The stabilizer (1) consists of three symmetric peptidic arms containing an arginine mimetic, previously described as the GCP motif. 1 stabilizes the 14-3-3?/ER? interaction synergistically with the natural product Fusicoccin-A and was thus hypothesized to bind to a different site. This is supported by computational analysis of 1 binding to the binary complex of 14-3-3 and an ER?-derived phosphopeptide. Furthermore, 1 shows selectivity towards 14-3-3?/ER? interaction over other 14-3-3 client-derived phosphomotifs. These data provide a solid support of a new binding mode for a supramolecular 14-3-3?/ER? PPI stabilizer.

SUBMITTER: Gigante A 

PROVIDER: S-EPMC7155037 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

A Supramolecular Stabilizer of the 14-3-3ζ/ERα Protein-Protein Interaction with a Synergistic Mode of Action.

Gigante Alba A   Sijbesma Eline E   Sánchez-Murcia Pedro A PA   Hu Xiaoyu X   Bier David D   Bäcker Sandra S   Knauer Shirley S   Gago Federico F   Ottmann Christian C   Schmuck Carsten C  

Angewandte Chemie (International ed. in English) 20200211 13

We report on a stabilizer of the interaction between 14-3-3ζ and the Estrogen Receptor alpha (ERα). ERα is a driver in the majority of breast cancers and 14-3-3 proteins are negative regulators of this nuclear receptor, making the stabilization of this protein-protein interaction (PPI) an interesting strategy. The stabilizer (1) consists of three symmetric peptidic arms containing an arginine mimetic, previously described as the GCP motif. 1 stabilizes the 14-3-3ζ/ERα interaction synergistically  ...[more]

Similar Datasets

Unknown Structure of the 14-3-3ζ-LKB1 fusion protein provides insight into a novel ligand-binding mode of 14-3-3.
| S-EPMC4555915 | biostudies-literature
Unknown Metabolic-stress-induced rearrangement of the 14-3-3ζ interactome promotes autophagy via a ULK1- and AMPK-regulated 14-3-3ζ interaction with phosphorylated Atg9.
| S-EPMC4248729 | biostudies-literature
Unknown Protein X-ray crystallography of the 14-3-3ζ/SOS1 complex.
| S-EPMC6141376 | biostudies-literature
Unknown Structure-Based Optimization of Covalent, Small-Molecule Stabilizers of the 14-3-3σ/ERα Protein-Protein Interaction from Nonselective Fragments.
| S-EPMC10515640 | biostudies-literature
Unknown Free energy calculations on the stability of the 14-3-3ζ protein.
| S-EPMC5881884 | biostudies-literature
Unknown [14-3-3ζ protein mediates gemcitabine resistance in NK/T-cell lymphoma].
| S-EPMC7342370 | biostudies-literature
Unknown Loss of Par3 promotes lung adenocarcinoma metastasis through 14-3-3ζ protein.
| S-EPMC5325440 | biostudies-literature
Unknown Role of 14-3-3ζ in platelet glycoprotein Ibα-von Willebrand factor interaction-induced signaling.
| S-EPMC3382782 | biostudies-literature
Unknown Structural Analysis of the 14-3-3ζ/Chibby Interaction Involved in Wnt/β-Catenin Signaling.
| S-EPMC4409382 | biostudies-literature
Unknown 14-3-3ζ coordinates adipogenesis of visceral fat.
| S-EPMC4532800 | biostudies-literature