Molecular mechanisms of intrinsically disordered proteins

Proteins are small nanomachines that carry out almost all tasks within a living cell: catalyzing enzymatic reactions, acting as pumps or motors, regulating gene expression, ... Besides the classically well-folded proteins, there exists another class of proteins that are intrinsically disordered. Most often these proteins or protein domains only adopt a folded structure upon interaction with a partner. Their intrinsically disordered nature facilitates a number of functions that would be difficult if not impossible for a protein with a pre-formed three-dimensional structure such as interacting with several structurally diverse partners. Here we propose bacterial toxin-antitoxin (TA) modules as model systems to study intrinsically unfolded proteins. In particular the ccdAB and parDE modules will be studied, both of which interfere with the action of gyrases as well as the mazEF and the phd/doc modules, which interferes with translation through either cutting mRNA or stalling the ribosome. The intrinsically unstructured domain of the antitoxins is crucial for counteracting their respective toxins and for regulation of expression of the operon. Thus we plan to study the mechanics of action of these TA modules in the light of intrinsic disorder and structural flexibility.