Szewczyk, Joanna
[UCL]
The bacterial envelope is a protective barrier that shelters the cell from its surroundings. This elaborate structure is made of the cytoplasmic membrane (CM), the outer membrane (OM) and the space between them called the periplasm. Several stress response systems exist in the envelope of the model bacterium E. coli that ensure efficient damage sensing and fast adaptation to hostile conditions. One of these systems is the Rcs, a complex cascade that responds to a wide variety of envelope defects. Despite its importance in the cell, the stress sensing mechanism used by the Rcs sensor component, the lipoprotein RcsF, remained elusive. Here I present the discovery of a unique molecular process that leads to triggering the Rcs response. We showed that RcsF detects envelope stress by monitoring the activity of the β-barrel assembly machinery (Bam). Under normal conditions the sensor lipoprotein is funneled by BamA, the core component of the Bam machinery, to β-barrel proteins, mostly OmpA. This process enables spatial separation between the OM-localized RcsF-containing complexes and CM-localized IgaA, the downstream Rcs cascade component. The interaction between RcsF and BamA is disrupted upon stress, which results in unobstructed access of RcsF to IgaA, triggering the response. To ensure correct functioning of the sensing process, RcsF must be targeted efficiently to the outer membrane. It is believed that lipoprotein sorting in E. coli envelope depends exclusively on the N-terminal amino acid residues in the lipoprotein’s sequence. I challenged this view by showing that the unstructured linker of RcsF and at least one other lipoprotein is essential for their efficient targeting within the envelope. These results not only change our view on lipoprotein sorting but also highlight the functional importance of disordered segments in proteins. Altogether, the above discoveries contributed substantially to our understanding of the bacterial envelope at the molecular level.
Bibliographic reference |
Szewczyk, Joanna. Escherichia coli stress sensor protein RcsF : stress sensing mechanism and subcellular targeting unraveled. Prom. : Collet, Jean-Francois |
Permanent URL |
http://hdl.handle.net/2078.1/177369 |