Domain Interactions Determine the Conformational Ensemble of the Periplasmic Chaperone Sura

SurA is thought to be the most important periplasmic chaperone for outer membrane protein (OMP) biogenesis. Its structure composed of a core region and two peptidylprolyl isomerase domains, termed P1 P2, connected by flexible linkers. As such these three independent folding units are able adopt number distinct spatial positions with respect each other. The conformational dynamics domains functionally yet largely unresolved. Here we address this question ensemble using sedimentation equilibrium, small-angle neutron scattering, titrations. This combination orthogonal methods converges on population that monomeric at physiological concentrations. conformation dominates has docked one another, example, "P1-closed" P2 domain extended in solution. We discovered distribution orientations defined modest favorable interactions between either or domains. These compete other core-binding but thermodynamically uncoupled. arrangement implies novel insights. Firstly, an open must exist facilitate exchange core, indicating client-binding populated low levels even absence client unfolded OMPs. Secondly, competition binding paradoxically occludes site which may serve preserve reservoir binding-competent apo-SurA periplasm.