Book of Abstracts: Albany 2005
Crystal Structure of Skp. A Prefoldin-like Chaperone that Prevents Protein Aggregation
The folding and insertion of outer membrane proteins (OMPs) in Gram-negative bacteria presents a topological problem. These proteins are synthesized in the cytosol and translocated across the inner membrane. However, OMPs need to be protected from aggregation and maintained in a folding/insertion competent form while transported through the aqueous periplasmic space. A periplasmic chaperone system aids OMP folding and insertion into the outer membrane. The Seventeen Kilodalton Protein (Skp, also known as OmpH and HlpA) is a molecular chaperone that interacts with proteins as they emerge from the translocation machinery and assists in delivery and correct insertion of OMPs into the outer membrane. We describe the crystal structure of Skp from E. coli, which resembles a jellyfish with α helical tentacles protruding from a β barrel body defining a central cavity. The architecture of Skp is unexpectedly similar to that of Prefoldin/GimC, a cytosolic chaperone present in eukarya and archea, that binds unfolded substrates in its central cavity. In contrast to many molecular chaperones, the ability of Skp to prevent the aggregation of model substrates in vitro is independent of ATP, and the structure does not show any ATP binding motifs. The independence of ATP is also shared with Prefoldin. A model for how Skp might prevent OMP aggregation in the periplasm and mediate the correct delivery and insertion of OMPs into the outer membrane will be discussed.
Troy A. Walton
Department of Chemistry and Biochemistry