Wang Xiaowen, Mbantenkhu MacMillan, Wierzbicki Sara, Chen Xin Jie
Department of Biochemistry and Molecular Biology, State University of New York Upstate Medical University, NY, USA.
J Vis Exp. 2013 Jun 25(76):50448. doi: 10.3791/50448.
The MGM101 gene was identified 20 years ago for its role in the maintenance of mitochondrial DNA. Studies from several groups have suggested that the Mgm101 protein is involved in the recombinational repair of mitochondrial DNA. Recent investigations have indicated that Mgm101 is related to the Rad52-type recombination protein family. These proteins form large oligomeric rings and promote the annealing of homologous single stranded DNA molecules. However, the characterization of Mgm101 has been hindered by the difficulty in producing the recombinant protein. Here, a reliable procedure for the preparation of recombinant Mgm101 is described. Maltose Binding Protein (MBP)-tagged Mgm101 is first expressed in Escherichia coli. The fusion protein is initially purified by amylose affinity chromatography. After being released by proteolytic cleavage, Mgm101 is separated from MBP by cationic exchange chromatography. Monodispersed Mgm101 is then obtained by size exclusion chromatography. A yield of ~0.87 mg of Mgm101 per liter of bacterial culture can be routinely obtained. The recombinant Mgm101 has minimal contamination of DNA. The prepared samples are successfully used for biochemical, structural and single particle image analyses of Mgm101. This protocol may also be used for the preparation of other large oligomeric DNA-binding proteins that may be misfolded and toxic to bacterial cells.
MGM101基因在20年前因其在线粒体DNA维持中的作用而被鉴定出来。多个研究小组的研究表明,MGM101蛋白参与线粒体DNA的重组修复。最近的研究表明,MGM101与Rad52型重组蛋白家族有关。这些蛋白形成大的寡聚环,并促进同源单链DNA分子的退火。然而,由于难以生产重组蛋白,MGM101的特性研究受到了阻碍。在此,描述了一种制备重组MGM101的可靠方法。带有麦芽糖结合蛋白(MBP)标签的MGM101首先在大肠杆菌中表达。融合蛋白最初通过直链淀粉亲和色谱法纯化。通过蛋白酶切割释放后,MGM101通过阳离子交换色谱法与MBP分离。然后通过尺寸排阻色谱法获得单分散的MGM101。每升细菌培养物通常可获得约0.87 mg的MGM101产量。重组MGM101的DNA污染最小。所制备的样品成功用于MGM101的生化、结构和单颗粒图像分析。该方案也可用于制备其他可能对细菌细胞错误折叠且有毒的大寡聚DNA结合蛋白。