Structure of the periplasmic chaperone Skp suggests functional similarity with cytosolic chaperones despite differing architecture

The 17-kDa protein (Skp) of Escherichia coli is a homotrimeric periplasmic chaperone for newly synthesized outer-membrane proteins. Here we present its X-ray structure at a resolution of 2.35 Å. Three hairpin-shaped aα-helical extensions reach out by ∼60 Å from a trimerization domain, which is composed of three intersubunit β-sheets that wind around a central axis. The α-helical extensions approach each other at their distal turns, resulting in a fold that resembles a 'three-pronged grasping forceps'. The overall shape of Skp is reminiscent of the cytosolic chaperone prefoldin, although it is based on a radically different topology. The peculiar architecture, with apparent plasticity of the prongs and distinct electrostatic and hydrophobic surface properties, supports the recently proposed biochemical mechanism of this chaperone: formation of a Skp₃-Omp complex protects the outer membrane protein from aggregation during passage through the bacterial periplasm.