Changing cellular location of CheZ predicted by molecular simulations.

Changing cellular location of CheZ predicted by molecular simulations.
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DOI:
10.1371/journal.pcbi.0020039
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发表时间:
2006-04
影响因子:
4.3
通讯作者:
Lipkow K
Lipkow K
中科院分区:
生物学2区
文献类型:
--
作者:
Lipkow K

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In the chemotaxis pathway of the bacterium Escherichia coli, signals are carried from a cluster of receptors to the flagellar motors by the diffusion of the protein CheY-phosphate (CheYp) through the cytoplasm. A second protein, CheZ, which promotes dephosphorylation of CheYp, partially colocalizes with receptors in the plasma membrane. CheZ is normally dimeric in solution but has been suggested to associate into highly active oligomers in the presence of CheYp. A model is presented here and supported by Brownian dynamics simulations, which accounts for these and other experimental data: A minority component of the receptor cluster (dimers of CheAshort) nucleates CheZ oligomerization and CheZ molecules move from the cytoplasm to a bound state at the receptor cluster depending on the current level of cellular stimulation. The corresponding simulations suggest that dynamic CheZ localization will sharpen cellular responses to chemoeffectors, increase the range of detectable ligand concentrations, and make adaptation more precise and robust. The localization and activation of CheZ constitute a negative feedback loop that provides a second tier of adaptation to the system. Subtle adjustments of this kind are likely to be found in many other signaling pathways. In order to function effectively, a living cell must not only synthesize the correct molecules but also put them in the correct place. Understanding how this positioning occurs, and what its consequences are, is a matter of great interest and concern to contemporary biologists. The author here proposes a novel mechanism that will enhance the ability of a bacterial cell to perform chemotaxis—the ability to swim toward sources of food or away from noxious substances. In this hypothesis, a key protein in the chemotaxis pathway moves dynamically between the membrane and the cytoplasm depending on the presence of attractants or repellents. This idea is explored and tested by means of detailed molecular simulations in which all of the relevant molecules are shown in their correct location in the cell. The simulations show that the proposed shift in location of the key molecule will improve the speed, range, and robustness of the cell's response. It seems likely that similar movements of proteins will occur in many other signaling pathways.
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发表时间: 1996-01-12
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