A Binary Bivalent Supramolecular Assembly Platform Based on Cucurbituril and Dimeric Adapter Protein 14-3-3
de Vink, P.J. and Briels, J.M. and Schrader, T. and Milroy, L.-G. and Brunsveld, L. and Ottmann, C.
ANGEWANDTE CHEMIE - INTERNATIONAL EDITION
Volume: 56 Pages: 8998-9002
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 cucurbituril (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. © 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.