Cucurbit[8]uril and 14-3-3 based binary bivalent supramolecular-protein assembly platform and co-crystal structure
 

Cucurbit[8]uril and 14-3-3 based binary bivalent supramolecular-protein assembly platform and co-crystal structure


Interactions between proteins frequently employ recognition sequences that engage in multivalent binding events. Dimeric 14-3-3 adapter proteins represent a prominent example, typically binding partner proteins in a phosphorylation-dependent mono- or bivalent manner. Here 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 ? (ER?), for selective binding to Q8. Q8-induced dimerization of the ER? epitope augmented its affinity towards 14-3-3 via a binary bivalent binding mode. The crystal structure of the Q8-induced ternary complex, a first of its kind, reveals molecular insights into the multiple supramolecular interactions between the protein, peptide and Q8.

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