Research group Tilman Schirmer
How do proteins communicate at the molecular level?
High-resolution structures reveal the mechanisms of signal transduction via the bacterial second messenger c-di-GMP and how the FIC domain can catalyze AMP transfer onto target proteins in a controlled way.
Proteins are a major component of cells and fulfill many different functions. We are using X-ray crystallography to determine their three-dimensional structures at the atomic level to deduce their mechanism of action.
How second messengers activate bacteria
Cyclic di-GMP, a small molecule composed of two nucleotides, acts as a transmitter in the bacterial cell. The concentration of the transmitter in the bacterial cell regulates bacterial life-style, in particular the transition from a sessility to mobility. Our research focuses on the enzymes responsible for the synthesis and breakdown of this transmitter, and on the down-stream c-di-GMP receptors. The spatial structures show how the activity of these enzymes is controlled by extrinsic signals, thus regulating the concentration of the transmitter in the cell. Elucidation of the molecular mechanism of this signaling pathway opens new ways for the development of drugs against bacterial pathogens.
How bacterial proteins disrupt signaling pathways in the host cells
Certain bacteria inject proteins into the host cell in order to alter cell function to their advantage. We are working on a newly discovered class of these so-called effector proteins that disable specific host proteins in a targeted manner by attachment of the small molecule AMP. Interestingly, the bacteria protect themselves from the action of these toxic proteins by producing an antitoxin. Structures show how this works and give new ideas how one could inactivate effector proteins within the host cell.