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Angew Chem Int Ed Engl. 2017 Jul 24;56(31):8998-9002. doi: 10.1002/anie.201701807. Epub 2017 Jun 29.

A Binary Bivalent Supramolecular Assembly Platform Based on Cucurbit[8]uril and Dimeric Adapter Protein 14-3-3.

Author information

1
Laboratory of Chemical Biology and Institute of Complex Molecular Systems, Department of Biomedical Engineering, Eindhoven University of Technology, Den Dolech 2, 5612 AZ, Eindhoven, The Netherlands.
2
Department of Chemistry, University of Duisburg-Essen, Universitätsstrasse 7, 45117, Essen, Germany.

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.

KEYWORDS:

adapter proteins; cooperativity; cucurbiturils; host-guest systems; supramolecular chemistry

PMID:
28510303
PMCID:
PMC5575475
DOI:
10.1002/anie.201701807
[Indexed for MEDLINE]
Free PMC Article

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