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

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 cuc...

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Detalles Bibliográficos
Autores principales: de Vink, Pim J., Briels, Jeroen M., Schrader, Thomas, Milroy, Lech‐Gustav, Brunsveld, Luc, Ottmann, Christian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5575475/
https://www.ncbi.nlm.nih.gov/pubmed/28510303
http://dx.doi.org/10.1002/anie.201701807
Descripción
Sumario: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.