Zylicz M, Ang D, Georgopoulos C
Department of Cellular, Viral, and Molecular Biology, University of Utah, Salt Lake City 84132.
J Biol Chem. 1987 Dec 25;262(36):17437-42.
The grpE gene of Escherichia coli was first identified because a mutation in it, grpE280, prevented bacteriophage lambda DNA replication in vivo. Subsequent work resulted in the identification of the grpE protein in two-dimensional gels and its classification as a heat shock protein. Here we report the purification of the grpE protein. We show that overproduction of grpE occurs in dnaK 103 bacteria which do not produce a functional Mr 72,000 dnaK protein. The grpE protein was purified from this strain primarily by its specific retention on a dnaK affinity column. The interaction between these two proteins, which is stable in the presence of 2 M KCl, allowed other proteins to be washed from this column. grpE was then eluted by ATP, which disrupts the interaction. During purification, grpE activity was monitored by its ability to complement an in vitro lambda dv DNA replication system dependent on the lambda O and lambda P proteins. The effect of ATP on the dnaK-grpE complex was also observed during sedimentation of the two proteins in glycerol gradients. Purified grpE protein has a Mr of approximately 23,000 under both denaturing and native conditions, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and sedimentation, respectively. However, in the presence of dnaK under native conditions, grpE cosediments with dnaK. When ATP is added to the gradient, the complex is disrupted, and the two proteins sediment independently as monomers.
大肠杆菌的grpE基因最初是因为其突变体grpE280在体内阻止噬菌体λDNA复制而被鉴定出来的。随后的研究工作使得在二维凝胶中鉴定出了grpE蛋白,并将其归类为热休克蛋白。在此我们报告grpE蛋白的纯化过程。我们发现,在不产生功能性72,000 Mr dnaK蛋白的dnaK 103细菌中会出现grpE的过量表达。grpE蛋白主要通过其在dnaK亲和柱上的特异性保留从该菌株中纯化出来。这两种蛋白质之间的相互作用在2 M KCl存在时是稳定的,使得其他蛋白质能够从该柱上被洗脱下来。然后通过ATP洗脱grpE,ATP会破坏这种相互作用。在纯化过程中,通过grpE补充依赖于λO和λP蛋白的体外λdv DNA复制系统的能力来监测其活性。在甘油梯度中对这两种蛋白质进行沉降时,也观察到了ATP对dnaK - grpE复合物的影响。通过十二烷基硫酸钠 - 聚丙烯酰胺凝胶电泳和沉降分别测定,纯化后的grpE蛋白在变性和天然条件下的Mr均约为23,000。然而,在天然条件下,当存在dnaK时,grpE与dnaK一起沉降。当向梯度中加入ATP时,复合物被破坏,这两种蛋白质作为单体独立沉降。