Oxidation State-dependent Protein-Protein Interactions in Disulfide Cascades
Oxidation State-dependent Protein-Protein Interactions in Disulfide Cascades
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DOI：
10.1074/jbc.m111.236141
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发表时间：
2011-07-15
影响因子：
4.8
通讯作者：
Redfield, Christina
中科院分区：
文献类型：
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作者：
Mavridou, Despoina A. I.;Saridakis, Emmanuel;Redfield, Christina
细菌的生长和致病性取决于二硫键的正确形成，这是由革兰氏阴性菌周质中的Dsb系统控制的过程。具有硫氧还蛋白折叠的蛋白质在此过程中起核心作用。硫醇-二硫化物交换反应的一般特征是需要避免蛋白质配偶体之间的长寿命产物复合物。我们使用多学科的方法，涉及NMR，X-射线晶体学，表面等离子体共振，诱变，和在体内实验，研究跨膜还原剂导体DsbD的两个可溶性结构域之间的相互作用。我们的研究结果表明，这两个域之间的氧化态依赖的亲和力。这些观察结果具有普遍存在的硫氧还蛋白样蛋白与其底物的相互作用的影响，提供了一个独特的氧化还原伙伴与免疫球蛋白折叠所发挥的关键作用的洞察力，并在所有生物体中的氧化蛋白折叠途径的普遍重要性。
Bacterial growth and pathogenicity depend on the correct formation of disulfide bonds, a process controlled by the Dsb system in the periplasm of Gram-negative bacteria. Proteins with a thioredoxin fold play a central role in this process. A general feature of thiol-disulfide exchange reactions is the need to avoid a long lived product complex between protein partners. We use a multidisciplinary approach, involving NMR, x-ray crystallography, surface plasmon resonance, mutagenesis, and in vivo experiments, to investigate the interaction between the two soluble domains of the transmembrane reductant conductor DsbD. Our results show oxidation state-dependent affinities between these two domains. These observations have implications for the interactions of the ubiquitous thioredoxin-like proteins with their substrates, provide insight into the key role played by a unique redox partner with an immunoglobulin fold, and are of general importance for oxidative protein-folding pathways in all organisms.