Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Gigante, A; Sijbesma, E; Sánchez-Murcia, PA; Hu, X; Bier, D; Bäcker, S; Knauer, S; Gago, F; Ottmann, C; Schmuck, C.
A Supramolecular Stabilizer of the 14-3-3ζ/ERα Protein-Protein Interaction with a Synergistic Mode of Action.
Angew Chem Int Ed Engl. 2020; 59(13):5284-5287
Doi: 10.1002/anie.201914517
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- Co-Autor*innen der Med Uni Graz
- Sánchez Murcia Pedro Alejandro
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- Abstract:
- 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 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 ERα-derived phosphopeptide. Furthermore, 1 shows selectivity towards 14-3-3ζ/ERα interaction over other 14-3-3 client-derived phosphomotifs. These data provide a solid support of a new binding mode for a supramolecular 14-3-3ζ/ERα PPI stabilizer. © 2019 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.
- Find related publications in this database (Keywords)
- 14-3-3
- ER alpha
- protein-protein interaction
- stabilizers
- supramolecular systems