New pathway found for regulating zinc in E. coli

E. coli is probably one of the most researched subjects in history!

"... researchers have discovered a pathway by which E. coli regulates all-important zinc levels, an insight that could advance the understanding of metal regulation in bacteria generally and lead to antibacterial applications such as in medical instruments and surgical settings. ...

E. coli have evolved mechanisms to bring in more zinc when it’s needed and to get rid of extra to avoid toxicity ... lab has discovered a previously unknown pathway the bacteria can use to control cellular zinc levels. 

The researchers found that the metal-regulating proteins Zur and ZntR – which control uptake and efflux (outflow), respectively – can cross-interact directly through the cell’s DNA, providing another way for the two metalloregulators to coordinate their actions as they control metal concentration in the cell. ...

Studying E. coli DNA, the researchers found that the DNA sequences Zur and ZntR recognize overlap partially, raising the question of whether they really can cross-interact. The experiment proving that they can was the first in-cell study of protein-DNA interaction kinetics as a function of concentration of two proteins.  ..."

From the abstract:

"Transition metals like Zn are essential for all organisms including bacteria, but fluctuations of their concentrations in the cell can be lethal. Organisms have thus evolved complex mechanisms for cellular metal homeostasis. One mechanistic paradigm involves pairs of transcription regulators sensing intracellular metal concentrations to regulate metal uptake and efflux.

Here we report that Zur and ZntR, a prototypical pair of regulators for Zn uptake and efflux in E. coli, respectively, can coordinate their regulation through DNA, besides sensing cellular Zn2+ concentrations. Using a combination of live-cell single-molecule tracking and in vitro single-molecule FRET measurements, we show that unmetallated ZntR can enhance the unbinding kinetics of Zur from DNA by directly acting on Zur-DNA complexes, possibly through forming heteromeric ternary and quaternary complexes that involve both protein-DNA and protein-protein interactions. This ‘through-DNA’ mechanism may functionally facilitate the switching in Zn-uptake regulation when bacteria encounter changing Zn environments, such as facilitating derepression of Zn-uptake genes upon Zn depletion; it could also be relevant for regulating the uptake-vs.-efflux of various metals across different bacterial species and yeast."

New pathway found for regulating zinc in E. coli | Cornell Chronicle

A ‘through-DNA’ mechanism for co-regulation of metal uptake and efflux

Fig. 2: Single-molecule tracking shows that ZntRapo enhances the kinetics of ZurZn unbinding from DNA in cells.