Protein flow in the bacterial cell envelope: sorting, folding, targeting and quality control

Proteins are made on microscopic factories inside cells. They come out as unstructured chains but must fold into defined 3D shapes to become functional. Occasionally, mis-folding causes diseases like Alzheimer's. Bacteria are surrounded by envelopes with hundreds of proteins that reach this compartment after crossing the cell's membrane. Exporting functional proteins to the envelope is an essential, complex process that is poorly understood. It is a two-way
communication: exported proteins carry bar-codes, while the cell combines channels, chaperones and guards that read the barcodes and guide hundreds of exported proteins to their final location. With fidelity. How do these remarkable processes operate successfully? To understand this, we use elaborate methods including stitching proteins together, determining their contours, stretching them to measure how tightly they interact and torches that blink when proteins come close. We aim to identify in which order chaperones and guards participate, how they recognize exported clients and which ones. This is challenging because
client recognition is promiscuous and brief. Also, stress changes the rules. However, by joining forces and expertise we can tackle this daunting task. Comprehending these amazing interactions teaches us how to exploit them to make vaccines and human drugs and inspires us to develop novel antibiotics. Enlightened by the inner workings of bacteria we can better understand mis-folding diseases in our cells.