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  Molecular tweezers modulate 14-3-3 protein–protein interactions

Bier, D., Rose, R., Bravo-Rodriguez, K., Bartel, M., Ramirez-Anguita, J. M., Dutt, S., et al. (2013). Molecular tweezers modulate 14-3-3 protein–protein interactions. Nature Chemistry, 5(3), 234-239. doi:10.1038/nchem.1570.

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Bier, David1, Author
Rose, Rolf1, Author
Bravo-Rodriguez, Kenny2, Author              
Bartel, Maria1, Author
Ramirez-Anguita, Juan Manuel2, Author              
Dutt, Som3, Author
Wilch, Constanze3, Author
Klärner, Frank-Gerrit3, Author
Sánchez-García, Elsa2, Author              
Schrader, Thomas3, Author
Ottman, Christian1, Author
Affiliations:
1Chemical Genomics Centre of the Max-Planck-Society, Otto-Hahn-Strasse 15, 44227 Dortmund, Germany, ou_persistent22              
2Research Group Sánchez-García, Max-Planck-Institut für Kohlenforschung, Max Planck Society, Kaiser-Wilhelm-Platz 1, 45470 Mülheim an der Ruhr, DE, ou_1950289              
3Department of Chemistry, University of Duisburg-Essen, Universita¨tsstrasse 7, 45117 Essen, Germany, ou_persistent22              

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Free keywords: Supramolecular chemistry; Chemical biology; Theoretical chemistry
 Abstract: Supramolecular chemistry has recently emerged as a promising way to modulate protein functions, but devising molecules that will interact with a protein in the desired manner is difficult as many competing interactions exist in a biological environment (with solvents, salts or different sites for the target biomolecule). We now show that lysine-specific molecular tweezers bind to a 14-3-3 adapter protein and modulate its interaction with partner proteins. The tweezers inhibit binding between the 14-3-3 protein and two partner proteins—a phosphorylated (C-Raf) protein and an unphosphorylated one (ExoS)—in a concentration-dependent manner. Protein crystallography shows that this effect arises from the binding of the tweezers to a single surface-exposed lysine (Lys214) of the 14-3-3 protein in the proximity of its central channel, which normally binds the partner proteins. A combination of structural analysis and computer simulations provides rules for the tweezers' binding preferences, thus allowing us to predict their influence on this type of protein–protein interactions.

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Language(s): eng - English
 Dates: 2012-06-212013-01-102013-02-172013-03
 Publication Status: Published in print
 Pages: 6
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1038/nchem.1570
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Title: Nature Chemistry
Source Genre: Journal
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Publ. Info: London, UK : Nature Publishing Group
Pages: 6 Volume / Issue: 5 (3) Sequence Number: - Start / End Page: 234 - 239 Identifier: ISSN: 1755-4330
CoNE: https://pure.mpg.de/cone/journals/resource/1755-4330