4HRU: Molecular Tweezers Modulate 14-3-3 Protein-protein Interactions

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.
PDB ID: 4HRUDownload
MMDB ID: 107978
PDB Deposition Date: 2012/10/28
Updated in MMDB: 2013/03
Experimental Method:
x-ray diffraction
Resolution: 3.15  Å
Source Organism:

*This structure record is obsolete.

Molecular Components in 4HRU
Label Count Molecule
Protein (1 molecule)
14-3-3 Protein Sigma
Molecule annotation
Chemicals (3 molecules)
* Click molecule labels to explore molecular sequence information.

Citing MMDB