Exploring the role of E. coli Skp in outer membrane biogenesis

Abstract

E. coli Seventeen Kilodalton Protein (Skp) is a trimeric molecular chaperone that is involved in outer membrane biogenesis. A Skp null mutant has been shown to increase outer membrane permeability and a reduction in outer membrane proteins has also been observed. Skp protects outer membrane proteins from aggregation in the periplasmic space and has been shown to increase the rate of folding of outer membrane protein A (OmpA) into lipid vesicles. This activity was dependant on the presence of the outer membrane component lipopolysaccharide (LPS). The structure of Skp was solved, and we identified a putative LPS binding site. Mutagenesis of the putative LPS binding site has been accomplished and data from these studies will be presented. The mechanism by which Skp is able to differentiate between the outer and inner membrane for substrate delivery is unknown. The lipid head groups exposed to the periplasmic space don’t suggest an obvious targeting determinant for Skp, which has been shown to interact with phospholipids. We are investigating the possibility that Skp interacts with a specific protein(s) in the outer membrane as a delivery site for its substrates.