Periplasmic folding factors in Gram-negative bacteria

Abstract

All organisms need a system to regulate the uptake of substances from their external milieu, allowing nutrients to enter and preventing toxic substances from doing so. In Gram-negative bacteria the cell envelope is responsible for determining which substances can enter the cell. It consists of two membranes, each with different selective permeability properties, and an aqueous space between the membranes known as the periplasm. Both the membranes and the periplasm contain many proteins which must adopt their correct three-dimensional structure in order to perform their crucial cellular functions. The periplasm of Gram-negative bacteria contains various folding factors that facilitate the folding of cell envelope proteins. These folding factors function by catalysing certain rate-limiting steps of the protein folding process (e.g. disulphide forming enzymes) or binding to unfolded or misfolded proteins and preventing them from aggregating (e.g. molecular chaperones). Studying these periplasmic folding factors is not only of fundamental interest to microbiologists and biochemists, but is also of importance to the fields of biotechnology, as protein folding is often a limiting factor in the production of biotechnological products, and medicine, as periplasmic folding factors could be potential drug targets. This thesis provides an overview of the current state of our knowledge on the functions and modes of action of periplasmic folding factors in Gram-negative bacteria. The main focus is on the periplasmic folding factors that have been identified in Escherichia coli, as this is a commonly studied model organism. The situation in other Gram-negative bacteria is also briefly discussed, as well as the perspectives for future research into periplasmic folding factors.