Decoding the non-folding code of preproteins secretion during Sec translocase targeting and secretion
The Sec secretion system is the general and essential protein export pathway across life. Its central component is the Sec translocase, a nanomachine that recognizes exported proteins and takes them out of cell membranes. Pathogenic bacteria use the Sec system to export proteins such as toxins. To control pathogenicity and exploit it for biopharmaceuticals production we need to understand how it works. Scientists have identified Sec components and we have previously determined essential novel signals that allow exported proteins to find it. We now propose a bold new step to take these studies to the next level by studying how these export signals are recognized as individual "stepping stones" by the nanomachine to push the preproteins out. For this we will use different tools including a translocation endoscope (exported proteins trapped during export that will be glued onto their surrounding nanomachine walls that can then be identified) and a light nanosensor (that blinks only when machine components come close). We aim to learn which components take part in the inner workings of the nanomachine, what is the order of events and how the nanomachine uses metabolic energy. This is a challenging goal as these tools have never been used before but we have the necessary expertise to tackle it. By better understanding the amazing Sec nanomachine we hope to inspire solutions for novel antibiotics, modern biotechnology and to understand protein conformational/trafficking diseases.