Genome Biology Unit, European Molecular Biology Laboratory, Heidelberg, Germany.
Faculty of Biology and Centre for Biological Signalling Studies (BIOSS), University of Freiburg, Germany.
FEBS Lett. 2018 Dec;592(24):4028-4038. doi: 10.1002/1873-3468.13284. Epub 2018 Nov 23.
Protein phosphatase-1 (PP1) drives a large amount of phosphoSer/Thr protein dephosphorylations in eukaryotes to counteract multiple kinases in signaling pathways. The phosphatase requires divalent metal cations for catalytic activity and contains iron naturally. Iron has been suggested to have an influence on PP1 activity through Fe and Fe oxidation states. However, much biochemical and all structural data have been obtained with recombinant PP1 containing Mn ions. Purifying iron-containing PP1 from Escherichia coli has thus far not been possible. Here, we present the preparation, characterization, and structure of iron-bound PP1α in inactive and active states. We establish a key role for the electronic/redox properties of iron in PP1 activity and shed light on the difference in substrate specificity between iron- and manganese-containing PP1.
蛋白磷酸酶-1（PP1）在真核生物中驱动大量磷酸丝氨酸/苏氨酸蛋白去磷酸化，以拮抗信号通路中的多种激酶。该磷酸酶需要二价金属阳离子才能发挥催化活性，天然含有铁。已经有人提出，铁的 Fe 和 Fe 氧化态对 PP1 活性有影响。然而，大多数生化和所有结构数据都是用含有锰离子的重组 PP1 获得的。从大肠杆菌中纯化含铁的 PP1 迄今尚未成功。在这里，我们介绍了非活性和活性状态下结合铁的 PP1α 的制备、表征和结构。我们确定了铁在 PP1 活性中的电子/氧化还原性质的关键作用，并阐明了含铁和含锰的 PP1 之间在底物特异性上的差异。
