Small proteins in bacterial signaling network
Our group focuses on the small proteins that involved in bacterial signaling. Specifically, we are interested in the regulation of the PhoQ/PhoP two-component system (TCS) by two small proteins, MgrB and SafA. The PhoQ/PhoP system is essential for magnesium homeostasis, host adaptation and virulence in enterobacteria. PhoQ senses host-associated stimuli including low magnesium, low pH, cationic antimicrobial peptides and osmotic upshift. The activated PhoQ sensor kinase autophosphorylates and then transfers the phosphate group to its cognate response regulator PhoP. The response regulator subsequently binds to specific gene promoters to regulate their expression, thus initiating cellular responses to environmental changes.
Two small proteins MgrB and SafA regulate the PhoQ/PhoP TCS by directly interacting with PhoQ. MgrB inhibits, while SafA activates PhoQ kinase activity. We investigate their regulations by monitoring PhoQ/small protein interactions, following signal integrations, identifying functionally important residues, mapping binding surfaces, and consequently designing peptide inhibitors to suppress bacterial virulence. Furthermore, we will identify other protein targets of MgrB and SafA and find out how small proteins connect different TCSs. To explore the mostly underinvestigated research field of small proteins, we use a collection of experimental approaches including FRET, microscopy, FACS analysis, genetics, proteomics, standard molecular biology techniques as well as simulations and crystallography via collaborations.