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.
Original language | English |
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Pages (from-to) | 8998-9002 |
Number of pages | 5 |
Journal | Angewandte Chemie - International Edition |
Volume | 56 |
Issue number | 31 |
DOIs | |
Publication status | Published - 24 Jul 2017 |
Keywords
- adapter proteins
- cooperativity
- cucurbiturils
- host–guest systems
- supramolecular chemistry