Departamento de Estructura de Macromoléculas, Centro Nacional de Biotecnología, CNB-CSIC, Darwin 3, 28049 Madrid, Spain.
J Biol Chem. 2013 May 24;288(21):15065-74. doi: 10.1074/jbc.M112.430595. Epub 2013 Apr 11.
Hsp40 chaperones bind and transfer substrate proteins to Hsp70s and regulate their ATPase activity. The interaction of Hsp40s with native proteins modifies their structure and function. A good model for this function is DnaJ, the bacterial Hsp40 that interacts with RepE, the repressor/activator of plasmid F replication, and together with DnaK regulates its function. We characterize here the structure of the DnaJ-RepE complex by electron microscopy, the first described structure of a complex between an Hsp40 and a client protein. The comparison of the complexes of DnaJ with two RepE mutants reveals an intrinsic plasticity of the DnaJ dimer that allows the chaperone to adapt to different substrates. We also show that DnaJ induces conformational changes in dimeric RepE, which increase the intermonomeric distance and remodel both RepE domains enhancing its affinity for DNA.
Hsp40 伴侣蛋白可结合并将底物蛋白转移到 Hsp70 上，并调节其 ATP 酶活性。Hsp40 与天然蛋白的相互作用可改变其结构和功能。DnaJ 是细菌 Hsp40 的一个很好的模型，它与 RepE（质粒 F 复制的阻遏物/激活物）相互作用，与 DnaK 一起调节其功能。我们通过电子显微镜描述了 DnaJ-RepE 复合物的结构，这是第一个描述 Hsp40 与客户蛋白之间复合物的结构。比较 DnaJ 与两个 RepE 突变体的复合物，揭示了 DnaJ 二聚体的固有可塑性，使伴侣蛋白能够适应不同的底物。我们还表明，DnaJ 诱导二聚体 RepE 的构象变化，增加了单体间的距离，并重塑了两个 RepE 结构域，增强了其与 DNA 的亲和力。
