Projects per year
Abstract
Cullin RING E3 ubiquitin ligases (CRLs) are large dynamic multi-subunit complexes that control the fate of many proteins in cells. CRLs constitute attractive drug targets for the development of small-molecule inhibitors and chemical inducers of protein degradation. Here we describe a structure-guided biophysical approach to probe the protein-protein interaction (PPI) between the Cullin-2 scaffold protein and the adaptor subunits Elongin BC within the context of the von Hippel-Lindau complex (CRL2VHL) using peptides. Two peptides were shown to bind at the targeted binding site on Elongin C, named the “EloC site”, with micromolar dissociation constants, providing a starting point for future optimization. Our results suggest ligandability of the EloC binding site to short linear peptides, unveiling the opportunity and challenges to develop small molecules that have the potential to target selectively the Cul2-adaptor PPI within CRLs.
Original language | English |
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Pages (from-to) | 1491-1496 |
Number of pages | 6 |
Journal | ChemMedChem |
Volume | 12 |
Issue number | 18 |
Early online date | 3 Aug 2017 |
DOIs | |
Publication status | Published - 21 Sept 2017 |
Keywords
- chemical probes
- Cullin RING E3 ligases
- peptides
- protein-protein interactions
- structure-guided design
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Dive into the research topics of 'Structure-guided design of peptides as tools to probe the protein-protein interaction between Cullin-2 and Elongin BC substrate adaptor in Cullin RING E3 ubiquitin ligases'. Together they form a unique fingerprint.Projects
- 1 Finished
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DrugE3CRL's: Probing Druggability of Multisubunit Complexes: E3 Cullin RING Ligases (ERC Starting Grant)
Ciulli, A. (Investigator)
COMMISSION OF THE EUROPEAN COMMUNITIES
1/05/13 → 30/04/18
Project: Research
Student theses
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Ligandability of protein-protein interactions and surfaces on Cullin RING E3 ubiquitin ligases
Cardote, T. A. D. F. (Author), Ciulli, A. (Supervisor), 2017Student thesis: Doctoral Thesis › Doctor of Philosophy
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