A binary bivalent supramolecular assembly platform based on Cucurbit[8]uril and Dimeric adapter protein 14-3-3

P.J. de Vink, J.M. Briels, T. Schrader, L.-G. Milroy, L. Brunsveld, C. Ottmann

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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.

Original languageEnglish
Pages (from-to)8998-9002
Number of pages5
JournalAngewandte Chemie - International Edition
Volume56
Issue number31
DOIs
Publication statusPublished - 24 Jul 2017

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14-3-3 Proteins
Proteins
Epitopes
Estrogen Receptors
Glycine
Amino acids
Phosphorylation
Dimerization
Phenylalanine
Dimers
Peptides
Crystal structure
cucurbit(8)uril

Keywords

  • Journal Article

Cite this

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title = "A binary bivalent supramolecular assembly platform based on Cucurbit[8]uril and Dimeric adapter protein 14-3-3",
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.",
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A binary bivalent supramolecular assembly platform based on Cucurbit[8]uril and Dimeric adapter protein 14-3-3. / de Vink, P.J.; Briels, J.M.; Schrader, T.; Milroy, L.-G.; Brunsveld, L.; Ottmann, C.

In: Angewandte Chemie - International Edition, Vol. 56, No. 31, 24.07.2017, p. 8998-9002.

Research output: Contribution to journalArticleAcademicpeer-review

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AU - de Vink, P.J.

AU - Briels, J.M.

AU - Schrader, T.

AU - Milroy, L.-G.

AU - Brunsveld, L.

AU - Ottmann, C.

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AB - 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.

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