Does functional misfolding of TonB drive import across the outer membrane of Gram negative bacteria?

Proteins carry out a wide-range of important functions that are essential for life, including the acquisition and metabolism of vital nutrients that are scarce in the environment. It is well accepted that, to be functional, most proteins need to fold to well a defined and stable three dimensional shape, known as their structure or conformation. More recently, however, proteins with no fixed structure or regions of no fixed structure called intrinsically disordered proteins (IDPs) or intrinsically disordered regions (IDRs) have emerged. These proteins play an important role in signalling by both responding to changes in the environment and by their ability to interact with a multitude of other proteins and other complex cellular molecules. As these proteins don't have a fixed structure and are very sensitive to even small changes in the environment, they are challenging to study and despite their importance, the precise way in which work is still being investigated. We have been studying a protein called TonB which contains an IDR that was thought to act merely as a passive linker between the two active parts of the protein at each end of this elongated protein. By stretching single protein molecules using an atomic force microscope we found that under some conditions this supposedly unstructured protein was able to resist extension (akin to a slip knot in a rope). The ability of TonB to toggle between a force-resistant, structured conformation and an unfolded conformation by changes in environment is completely novel and understanding how this works may help to understand a long standing question of how bacteria acquire some nutrients.

The import of nutrients is problematic for a large class of bacteria (Gram negative) which have a protective barrier outside their cell membrane called the outer membrane. While allowing their survival in harsh conditions, the outer membrane also acts as a barrier to the import of large nutrients. As there is no energy source in the...