Chaperone Spy Protects Outer Membrane Proteins from Folding Stress via Dynamic Complex Formation
Wei He, Gangjin Yu, Tianpeng Li, Ling Bai, Yuanyuan Yang, Zixiao Xue, Yonghao Pang, Dana Reichmann, Sebastian Hiller, Lichun He, Maili Liu, Shu Quan
Abstract
Outer membrane proteins (OMPs) play critical roles in bacterial pathogenicity and provide a new niche for antibiotic development. A comprehensive understanding of the OMP quality control network will strongly impact antimicrobial discovery. Here, we systematically demonstrate that the periplasmic chaperone Spy has a role in maintaining the homeostasis of certain OMPs. Remarkably, Spy utilizes a unique chaperone mechanism to bind OmpX and allows it to form a partially folded β-strand secondary structure in a dynamic exchange of conformations. This mechanism differs from that of other E. coli periplasmic chaperones such as Skp and SurA, both of which maintain OMPs in disordered conformations. Our study thus deepens the understanding of the complex OMP quality control system and highlights the differences in the mechanisms of ATP-independent chaperones.