Angewandte Chemie International Edition

德国应用化学

Visualizing an Ultra-Weak Protein–Protein Interaction in  Phosphorylation Signaling

QiongXing, Peng Huang,Ju Yang, Jian-Qiang Sun, Zhou Gong, Xu Dong, Da-Chuan Guo,Shao-Min Chen,

Yu-Hong Yang, Yan Wang, Ming-Hui Yang, Ming Yi,Yi-Ming Ding, Mai-Li Liu, Wei-Ping Zhang*, Chun Tang*    

Abstract: Proteins interact with each other to fulfill their
functions. The importance of weak protein–protein interactions
has been increasingly recognized. However, owing to
technical difficulties, ultra-weak interactions remain to be
characterized. Phosphorylation can take place via a KD
25 mm interaction between two bacterial enzymes. Using
paramagnetic NMR spectroscopy and with the introduction of
a novel GdIII-based probe, we determined the structure of the
resulting complex to atomic resolution. The structure accounts
for the mechanism of phosphoryl transfer between the two
enzymes and demonstrates the physical basis for their ultraweak
interaction. Further, molecular dynamics (MD) simulations
suggest that the complex has a lifetime in the micro- to
millisecond regimen. Hence such interaction is termed a fleeting
interaction. From mathematical modeling, we propose that an
ultra-weak fleeting interaction enables rapid flux of phosphoryl
signal, providing a high effective protein concentration