A Binary Bivalent Supramolecular Assembly Platform Based on Cucurbit[8]uril and Dimeric Adapter Protein 14‐3‐3. Issue 31 (29th June 2017)

• Record Type: Journal Article
• Authors: de Vink, Pim J.; Briels, Jeroen M.; Schrader, Thomas; Milroy, Lech‐Gustav; Brunsveld, Luc; Ottmann, Christian
• Is Part Of: Angewandte Chemie international edition. Volume 56:Issue 31(2017)
• Page Start: 8998
• Page End: 9002
• Publication Date: 2017-06-29
• Subjects: adapter proteins -- cooperativity -- cucurbiturils -- host–guest systems -- supramolecular chemistry; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201701807
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: Interactions between proteins frequently involve recognition sequences based on multivalent binding events. Dimeric 14‐3‐3 adapter proteins are a prominent example and typically bind partner proteins in a phosphorylation‐dependent mono‐ or bivalent manner. Herein we describe the development of a cucurbit[8]uril (Q8)‐based supramolecular system, which in conjunction with the 14‐3‐3 protein dimer acts as a binary and bivalent protein assembly platform. We fused the phenylalanine–glycine–glycine (FGG) tripeptide motif to the N‐terminus of the 14‐3‐3‐binding epitope of the estrogen receptor α (ERα) for selective binding to Q8. Q8‐induced dimerization of the ERα epitope augmented its affinity towards 14‐3‐3 through a binary bivalent binding mode. The crystal structure of the Q8‐induced ternary complex revealed molecular insight into the multiple supramolecular interactions between the protein, the peptide, and Q8. Abstract : Binary bivalent binding : The combination of a bivalent cucurbit[8]uril (Q8) host–guest complex with the bivalent protein 14‐3‐3 generated a binary assembly platform. Supramolecular induced switching between mono‐ and bivalent protein modes was observed and the elucidation of the first Q8‐protein cocrystal structure reported.