Interaction of substrates with the E.coli Tat protein export system (360G-Wellcome-089692_Z_09_Z)

The overall aim of this project is to characterise the interactions of Tat substrates with signal peptide binding chaperones and with the TatBC receptor complex, with the intent of using the findings to guide development of assays that can be used in high throughput screening of small drug-like molecules targeting TatBC signal peptide binding. The project will be split into three specific objectives: I. Structural characterisation of the Tat substrate Tor A in complex with its signal peptide binding chaperone TorD using the E. coli and homologous Salmonella protein pairs and using modem structural biology techniques. 2. Investigation of how substrates are handed over to the TatBC complex and development of in vivo and in vitro assays to measure this. 3. Development of an in vitro assay to assess substrate interaction with the TatBC complex that will be used to screen for small molecule inhibitors.