New Genetics Approaches for Understanding Protein Folding and Membrane Translocation
in Bacteria

2006 Dale Pearson Lectures
Presented by

Professor George Georgiou
University of Texas, Austin

Date: Tuesday
April 4, 2006
4:00 p.m.
Place: Engineering Sciences Building
ESB Room 1001

ABSTRACT

A long term interest in our lab has been the understanding of how proteins move across lipid bilayer membranes and the relationship between protein secretion and folding. Our interest in high throughput screening techniques has greatly facilitated the development of new tools for genetic analysis that in turn have allowed us to address several complex problems in protein biogenesis.

The majority of proteins are secreted across the lipid bilayer membrane by “snaking through” a narrow protein pore. However, eight years ago it was found that a subset of proteins first reach their globular three dimensional structure and then transverse the membrane in a folded conformation. Remarkably, protein translocation is not accompanied by the leakage of small molecules and ions, an event which would be detrimental to the cell. This process of protein secretion is called the twin arginine translocation pathway (Tat) and its mechanism remains largely unknown. Using genetic analysis we have: (i) identified the first step in translocation; (ii) determined what proteins are exported via this route and (iii) demonstrated that unfolded proteins cannot cross the membrane via Tat. Also we have exploited this mechanistic information to develop new techniques for protein discovery and production.