Substrate-receptor interactions in the Tat protein transport pathway

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All bacteria produce proteins that operate on the outside of the bacterial cell. Good examples of this are the toxins produced by bacterial pathogens. Since bacteria only make proteins inside the cell, the newly-synthesised extracellular proteins must be moved out of the cell across the normally impermeable cell membrane. This task is carried out by machines termed protein transporters that are located in the cell membrane. The Tat protein transporter is found in many different bacteria including almost all those which cause human diseases such as Mycobacterium tuberculosis (which causes tuberculosis), and Salmonella (which causes food poisoning). In all pathogenic bacteria tested the Tat transporter is essential for the bacterium to cause disease. Thus, scientists are becoming increasingly interested in developing drugs that prevent the Tat system from working. In order to understand how the Tat machinery works, and ultimately to design new drugs to stop it working, this project will use cutting edge technology to elucidate how the transport machinery recognises the targeting tags present on the proteins that are to be transported. We will also test the hypothesis that the Tat transporter works by moving the tag across the membrane and that this pulls the passenger protein after it.