Premium
A Binary Bivalent Supramolecular Assembly Platform Based on Cucurbit[8]uril and Dimeric Adapter Protein 14‐3‐3
Author(s) -
de Vink Pim J.,
Briels Jeroen M.,
Schrader Thomas,
Milroy LechGustav,
Brunsveld Luc,
Ottmann Christian
Publication year - 2017
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201701807
Subject(s) - supramolecular chemistry , chemistry , dimer , bivalent (engine) , signal transducing adaptor protein , tripeptide , supramolecular assembly , protein–protein interaction , crystallography , peptide , stereochemistry , biochemistry , crystal structure , phosphorylation , organic chemistry , metal
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.