Andresen Cecilia, Niklasson Markus, Cassman Eklöf Sofie, Wallner Björn, Lundström Patrik
Division of Chemistry, Department of Physics, Chemistry and Biology, Linköping University, Linköping, Sweden.
Division of Bioinformatics, Department of Physics, Chemistry and Biology, Linköping University, Linköping, Sweden.
PLoS One. 2017 Jul 26;12(7):e0181721. doi: 10.1371/journal.pone.0181721. eCollection 2017.
Calcium dependent protein kinases are unique to plants and certain parasites and comprise an N-terminal segment and a kinase domain that is regulated by a C-terminal calcium binding domain. Since the proteins are not found in man they are potential drug targets. We have characterized the calcium binding lobes of the regulatory domain of calcium dependent protein kinase 3 from the malaria parasite Plasmodium falciparum. Despite being structurally similar, the two lobes differ in several other regards. While the monomeric N-terminal lobe changes its structure in response to calcium binding and shows global dynamics on the sub-millisecond time-scale both in its apo and calcium bound states, the C-terminal lobe could not be prepared calcium-free and forms dimers in solution. If our results can be generalized to the full-length protein, they suggest that the C-terminal lobe is calcium bound even at basal levels and that activation is caused by the structural reorganization associated with binding of a single calcium ion to the N-terminal lobe.
钙依赖性蛋白激酶是植物和某些寄生虫所特有的，由一个N端结构域和一个激酶结构域组成，该激酶结构域受C端钙结合结构域的调控。由于这些蛋白质在人类中不存在，它们是潜在的药物靶点。我们已经对疟原虫恶性疟原虫钙依赖性蛋白激酶3调节结构域的钙结合叶进行了表征。尽管在结构上相似，但这两个叶在其他几个方面有所不同。单体N端叶在结合钙时会改变其结构，并且在其无钙和钙结合状态下均在亚毫秒时间尺度上表现出整体动力学，而C端叶无法制备成无钙状态，并且在溶液中形成二聚体。如果我们的结果可以推广到全长蛋白，那么它们表明C端叶即使在基础水平也结合钙，并且激活是由与单个钙离子结合到N端叶相关的结构重组引起的。
