title: Visualizing an ultra-weak protein-protein interaction in phosphorylation signaling.
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 K(D)≈25 mM 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.
authors.affiliation: CAS Key Laboratory of Magnetic Resonance in Biological Systems, Wuhan Center for Magnetic Resonance, State Key Laboratory of Magnetic Resonance and Atomic Molecular Physics, Wuhan Institute of Physics and Mathematics of the Chinese Academy of Sciences, Xiao-Hong Shan, Wuhan, Hubei 430071 (China) http://tanglab.wipm.ac.cn.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Xing
authors.forename: Peng
authors.initials: P
authors.lastname: Huang
authors.forename: Ju
authors.initials: J
authors.lastname: Yang
authors.forename: Jian-Qiang
authors.initials: JQ
authors.lastname: Sun
authors.forename: Zhou
authors.initials: Z
authors.lastname: Gong
authors.forename: Xu
authors.initials: X
authors.lastname: Dong
authors.forename: Da-Chuan
authors.initials: DC
authors.lastname: Guo
authors.forename: Shao-Min
authors.initials: SM
authors.lastname: Chen
authors.forename: Yu-Hong
authors.initials: YH
authors.lastname: Yang
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Ming-Hui
authors.initials: MH
authors.lastname: Yang
authors.forename: Ming
authors.initials: M
authors.lastname: Yi
authors.forename: Yi-Ming
authors.initials: YM
authors.lastname: Ding
authors.forename: Mai-Li
authors.initials: ML
authors.lastname: Liu
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Zhang
authors.forename: Chun
authors.initials: C
authors.lastname: Tang
mesh_terms: D056004:Molecular Dynamics Simulation; D019906:Nuclear Magnetic Resonance, Biomolecular; D010766:Phosphorylation; D011506:Proteins / Q000737:chemistry*; D015398:Signal Transduction
chemical_list: D011506:Proteins
keywords: NMR spectroscopy; paramagnetic relaxation enhancement; protein-protein interactions; proteins; signal transduction