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Visualizing an Ultra‐Weak Protein–Protein Interaction in Phosphorylation Signaling
Author(s) -
Xing Qiong,
Huang Peng,
Yang Ju,
Sun JianQiang,
Gong Zhou,
Dong Xu,
Guo DaChuan,
Chen ShaoMin,
Yang YuHong,
Wang Yan,
Yang MingHui,
Yi Ming,
Ding YiMing,
Liu MaiLi,
Zhang WeiPing,
Tang Chun
Publication year - 2014
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201405976
Subject(s) - protein–protein interaction , chemistry , phosphorylation , molecular dynamics , protein dynamics , complex formation , biophysics , nuclear magnetic resonance spectroscopy , protein structure , chemical physics , computational chemistry , biochemistry , stereochemistry , biology , inorganic chemistry
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 K D ≈25 m M interaction between two bacterial enzymes. Using paramagnetic NMR spectroscopy and with the introduction of a novel Gd III ‐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 ultra‐weak 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.