Small proteins in bacterial signaling networks
Dr. Jing Yuan
Small proteins are generally less than 50 amino acids long, directly translated from small open reading frame by ribosomes and regulate wide varieties of cellular processes. Hundreds of small proteins have been recently identified in bacteria and thousands in eukaryotes, indicating their abundance and diversity in living cells as well as opening up a whole new field of research. Our group focuses on the small proteins that are involved in bacterial signaling.
The major signaling pathways for bacteria to sense and adapt to the changing environment are bacterial two-component systems (TCSs). They are essential for pathogenic bacteria to survive and invade their host. A typical two-component system consists of a membrane located sensor kinase and a cytosolic response regulator. When the sensor kinase gets activated by an environmental stimulus, it phosphorylates the response regulator, which in turn binds to target DNA regions, and regulates gene expressions. E. coli and Salmonella have about 30 TCSs. The small proteins we currently study regulate a TCS and modulate bacterial virulence. Using both in vivo and in vitro experimental approaches in combination with computational simulations, we aim to answer the following questions:
- What are the regulation mechanisms of small proteins?
- How does nature orchestrate antagonistic regulations?
- Can we design small proteins to suppress the virulence of drug-resistant bacteria?
- Does one small protein have multiple targets?
Yuan J*, Jin F, Glatter T, Sourjik V*. (2017)
Osmosensing by the bacterial PhoQ/PhoP two-component system. Proc. Natl. Acad. Sci. USA, 114 (50): E10792-10798. (*Corresponding authors)
Liu Y, Dos Santos PC, Zhu X, Orlando R, Dean DR, Söll D, Yuan J. (2012)
Catalytic mechanism of Sep-tRNA:Cys-tRNA synthase: sulfur transfer is mediated by disulfide and persulfide. J Biol Chem, 287, 5426-5433.
Yuan J, Gogakos T, Babina AM, Söll D, Randau L. (2011)
Change of tRNA identity leads to a divergent orthogonal histidyl-tRNA synthetase/tRNAHis pair. Nucleic Acids Res, 39, 2286-2293.
Yuan J, Hohn MJ, Sherrer RL, Palioura S, Su D, Söll D. (2010)
A tRNA-dependent cysteine biosynthesis enzyme recognizes the selenocysteine-specific tRNA in Escherichia coli. FEBS Lett, 584, 2857-2861.