Visualization of transient encounter complexes in protein-protein association

被引:336
作者
Tang, Chun [1 ]
Iwahara, Junji [1 ]
Clore, G. Marius [1 ]
机构
[1] NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA
关键词
D O I
10.1038/nature05201
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Kinetic data on a number of protein - protein associations have provided evidence for the initial formation of a pre- equilibrium encounter complex that subsequently relaxes to the final stereospecific complex (1). Site- directed mutagenesis(2 - 4) and brownian dynamics simulations(5 - 7) have suggested that the rate of association can be modulated by perturbations in charge distribution outside the direct interaction surfaces. Furthermore, rate enhancement through non- specific binding may occur by either a reduction in dimensionality(8) or the presence of a short- range, non- specific attractive potential(9). Here, using paramagnetic relaxation enhancement, we directly demonstrate the existence and visualize the distribution of an ensemble of transient, non- specific encounter complexes under equilibrium conditions for a relatively weak protein - protein complex between the amino- terminal domain of enzyme I and the phosphocarrier protein HPr. Neither the stereospecific complex(10) alone nor any single alternative conformation can account fully for the intermolecular paramagnetic relaxation enhancement data. Restrained rigid- body simulated annealing refinement against the paramagnetic relaxation enhancement data enables us to obtain an atomic probability distribution map of the non- specific encounter complex ensemble that qualitatively correlates with the electrostatic surface potentials on the interacting proteins. Qualitatively similar results are presented for two other protein - protein complexes.
引用
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页码:383 / 386
页数:4
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