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

中文翻译：

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结构域相互作用决定了周质伴侣 SurA 的构象整体。


SurA 被认为是外膜蛋白 (OMP) 生物合成中最重要的周质伴侣。其结构由一个核心区域和两个肽基脯氨酰异构酶结构域（称为 P1 和 P2）组成，通过柔性接头连接。因此，这三个独立的折叠单元能够采用多个彼此不同的空间位置。这些结构域的构象动力学被认为具有重要的功能，但在很大程度上尚未得到解决。在这里，我们使用沉降平衡、小角中子散射和折叠滴定来解决构象系综的问题。这种正交方法的组合收敛于在生理浓度下为单体的 SurA 群体。主导这一群体的构象具有彼此对接的 P1 和核心结构域，例如“P1 闭合”和在溶液中延伸的 P2 结构域。我们发现域方向的分布是由核心域与 P1 或 P2 域之间适度且有利的相互作用定义的。这两个肽基脯氨酰结构域相互竞争核心结合，但在热力学上是解偶联的。这种安排意味着两个新颖的见解。首先，必须存在开放构象以促进核心上的 P1 和 P2 交换，这表明即使在没有客户端展开的 OMP 的情况下，开放的客户端绑定构象也会以较低的水平填充。其次，P1 和 P2 结合之间的竞争矛盾地封闭了核心上的客户结合位点，这可能有助于保留周质中具有结合能力的 apo-SurA 的储存库。