Elucidation of the Structure and function of a novel Sec component

Sec-dependent translocation of proteins across the cytoplasmic membrane is a fundamental and evolutionarily conserved biological process. Over the past 40 years, the core Sec machinery in bacteria has been investigated extensively. However, recent work by the Huber group has identified a novel accessory component to the Sec pathway, AscA (YecA). Our research suggests that AscA is a molecular chaperone that recognises its nascent substrate proteins as they are still being synthesised (i.e. cotranslationally). AscA then targets these substrate proteins for translocation by interacting with a component of the Sec machinery, probably SecB. However, the structural basis for substrate protein recognition is unknown. The goal of this project is to determine the structure of AscA and to determine the molecular mechanism of substrate protein recognition at the structural and biochemical level. The project will use a combination of methodologies including structural biology (predominantly NMR, but potentially also x-ray crystallography) and molecular biology to address these aims. This is fundamental underpinning bioscience research. However, it also has important implications for bacterial protein production and will therefore be of interest to biotechnology.