orals 5th Asia-Pacific NMR Symposium 2013

Visualizing Fleeting Protein-Protein Interactions using PRE NMR (#74)

Chun Tang 1
  1. Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan, Hubei, China

Many biophysical methods can detect protein-protein interactions, though most of them only work for strong interactions. Binding events with dissociation constant (KD) in µM regimen are generally considered weak transient – nuclear magnetic resonance (NMR) is uniquely suited to characterize such weak interactions. By evaluating intermolecular nuclear Overhauser effect (NOE), protein complexes with KD values up to ~1mM can be characterized. As to develop new technologies for identifying even weaker protein-protein interactions, a related question is how weak the interactions can be. Here I will present that phosphorylation signalling can be accomplished with a fleeting complex between two enzymes with KD value of ~25mM. Using paramagnetic relaxation enhancement (PRE), a technique that is exquisitely sensitive to protein fleeting encounter, and by specifically introducing a Gd3+-based probe, we were able to visualize the structure of the complex, which is converged to a unique conformation. This structure readily accounts for phosphoryl transfer between the two proteins, and our study lays the foundation for assessing other fleeting complexes. Although weak for freely diffusing encounters, protein-protein interactions can be boosted inside a cell, thus to achieve a fine balance between association and dissociation.