Unknown

Dataset Information

0

The response threshold of Salmonella PilZ domain proteins is determined by their binding affinities for c-di-GMP.


ABSTRACT: c-di-GMP is a bacterial second messenger that is enzymatically synthesized and degraded in response to environmental signals. Cellular processes are affected when c-di-GMP binds to receptors which include proteins that contain the PilZ domain. Although each c-di-GMP synthesis or degradation enzyme metabolizes the same molecule, many of these enzymes can be linked to specific downstream processes. Here we present evidence that c-di-GMP signalling specificity is achieved through differences in affinities of receptor macromolecules. We show that the PilZ domain proteins of Salmonella Typhimurium, YcgR and BcsA, demonstrate a 43-fold difference in their affinity for c-di-GMP. Modulation of the affinities of these proteins altered their activities in a predictable manner in vivo. Inactivation of yhjH, which encodes a predicted c-di-GMP degrading enzyme, increased the fraction of the cellular population that demonstrated c-di-GMP levels high enough to bind to the higher-affinity YcgR protein and inhibit motility, but not high enough to bind to the lower-affinity BcsA protein and stimulate cellulose production. Finally, PilZ domain proteins of Pseudomonas aeruginosa demonstrated a 145-fold difference in binding affinities, suggesting that regulation by binding affinity may be a conserved mechanism that allows organisms with many c-di-GMP binding macromolecules to rapidly integrate multiple environmental signals into one output.

SUBMITTER: Pultz IS 

PROVIDER: S-EPMC5034864 | biostudies-literature | 2012 Dec

REPOSITORIES: biostudies-literature

altmetric image

Publications

The response threshold of Salmonella PilZ domain proteins is determined by their binding affinities for c-di-GMP.

Pultz Ingrid Swanson IS   Christen Matthias M   Kulasekara Hemantha Don HD   Kennard Andrew A   Kulasekara Bridget B   Miller Samuel I SI  

Molecular microbiology 20121119 6


c-di-GMP is a bacterial second messenger that is enzymatically synthesized and degraded in response to environmental signals. Cellular processes are affected when c-di-GMP binds to receptors which include proteins that contain the PilZ domain. Although each c-di-GMP synthesis or degradation enzyme metabolizes the same molecule, many of these enzymes can be linked to specific downstream processes. Here we present evidence that c-di-GMP signalling specificity is achieved through differences in aff  ...[more]

Similar Datasets

| S-EPMC4475898 | biostudies-literature
| S-EPMC4907108 | biostudies-literature
| S-EPMC3077631 | biostudies-literature
| S-EPMC4686193 | biostudies-literature
| S-EPMC10657408 | biostudies-literature
| S-EPMC5018759 | biostudies-literature
| S-EPMC5013675 | biostudies-literature
2023-08-05 | GSE239303 | GEO
| S-EPMC4624772 | biostudies-literature
| S-EPMC5474780 | biostudies-literature