Bacterial Genes & Development: Two-Component Signaling and Osmolarity Regulation Summary

Sensor regulator pairs: sensor (membrane-associated) and regulator (small, soluble).
Sensor transduces environmental changes into regulator activation via conformational changes and kinase activity.
Activated, phosphorylated regulator alters transcription of specific genes.
Histidine kinase (HK) phosphorylates itself on Histidine (H), then phosphorylates a response regulator (RR) on Aspartate (D).
Phosphorylation alters regulator conformation, changing its affinity for promoter elements.
Kinases are dimers that bind ATP and transfer it to Histidine, then to response regulator.
Specificity is determined by signaling regions on HK and RR.

Different sensors perceive diverse stimuli and transmit signals to correct regulators.
Amino-acid sequences of each pair are evolved to specialize as “signaling regions”.
Experimental evidence: Labeled kinases transfer phosphate to the correct regulator.
Contact amino-acids in two-component pairs co-evolve to preserve specific contact.
Pathway insulation: evolved following gene duplication so one HK signals specifically to one RR via their specificity residues

EnvZ-OmpR controls expression of E. coli porins (OmpF or OmpC) in response to osmolarity.
Osmolarity: measure of dissolved substances in a solution.
Porins: channels in the outer membrane that allow molecules of a certain size to diffuse in.
OmpC (small pore): expressed under high osmolarity.
OmpF (large pore): expressed under low osmolarity, repressed under high osmolarity and high temperature.
EnvZ senses osmolarity and acts as a kinase at high osmolarity, phosphorylating OmpR.
OmpR-P binds to ompC promoter (low affinity) to activate transcription and to ompF promoter (low affinity) to repress transcription.
At low osmolarity, EnvZ can act as an OmpR-P-phosphatase, balancing its levels.