Structural Insights into the Chaperone Activity of the 40-kDa Heat Shock Protein DnaJ BINDING AND REMODELING OF A NATIVE SUBSTRATE
Structural Insights into the Chaperone Activity of the 40-kDa Heat Shock Protein DnaJ BINDING AND REMODELING OF A NATIVE SUBSTRATE
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DOI：
10.1074/jbc.m112.430595
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发表时间：
2013-05-24
影响因子：
4.8
通讯作者：
Moro, Fernando
中科院分区：
文献类型：
--
作者：
Cuellar, Jorge;Perales-Calvo, Judit;Moro, Fernando
Hsp40伴侣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改变了它们的结构和功能。这种功能的一个很好的模型是DnaJ，细菌Hsp40与质粒F复制的抑制因子/激活因子RepE相互作用，并与DnaK一起调节其功能。我们通过电子显微镜表征了DnaJ-RepE复合物的结构，这是第一个描述的Hsp40和客户蛋白之间复合物的结构。DnaJ复合物与两个突变体的比较揭示了DnaJ二聚体的内在可塑性，使伴侣能够适应不同的底物。我们还发现，DnaJ诱导二聚体RepE的构象变化，增加了RepE的单体间距离，重塑了RepE的两个结构域，增强了其对DNA的亲和力。
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.