LAUSR

The periplasmic protein SurA is the primary chaperone involved in the biogenesis of bacterial outer membrane proteins (OMPs) and is a potential antibacterial drug target. The three-dimensional structure of SurA can be divided into three parts, a core module formed by the N- and C- terminal regions, and two peptidyl-prolyl isomerase (PPIase) domains P1 and P2. Despite the determination of several SurA-peptide complex structures, the functional mechanism of this chaperone remains elusive and the roles of the two PPIase domains are yet unclear. Herein, we characterize the conformational dynamics of SurA by using solution NMR and single-molecule fluorescence resonance energy transfer (smFRET) methods. We demonstrate a "closed-to-open" structural transition of the P1 domain that is correlated with both chaperone activity and peptide binding, and show that the flexible P2 domain can also occupy conformations that closely contact the NC core module. Our results offer the structural basis for the counteracting roles of the two PPIase domains in regulating the SurA chaperone activity.