Chaperones Skp and SurA dynamically expand unfolded OmpX and synergistically disassemble oligomeric aggregates

Abstract

Significance Outer membrane proteins (OMPs) are crucial for the survival of bacteria. The two chaperones 17-kilodalton protein (Skp) and survival factor A (SurA) play key roles in OMP maturation by keeping unfolded OMP proteins soluble in the periplasm. However, their functionalities are incompletely understood. Here, we establish connections between structural and energetic features employed by the two chaperones when interacting with unfolded OmpX. We find that expansion, accompanied with fast polypeptide chain reconfiguration, prevents unfolded OmpX from misfolding and aggregating. Moreover, chaperone interaction with unfolded OmpX is thermodynamically calibrated, allowing for a fine-tuned association of chaperones with OMPs in the adenosine triphosphate-depleted periplasm. We further discovered that Skp and SurA act together as disaggregases and are able to disassemble oligomeric OMP aggregates, revealing remarkable functionalities of this periplasmic chaperone system.