Prescott M, Lourbakos A, Bateson M, Boyle G, Nagley P, Devenish R J
Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia.
FEBS Lett. 1997 Jul 7;411(1):97-101. doi: 10.1016/s0014-5793(97)00670-4.
We have shown that OSCP, a subunit of yeast mitochondrial ATP synthase, can be incorporated into the intact enzyme as a fusion protein representing OSCP fused at its C-terminus to the green fluorescent protein (GFP) of Aequorea victoria. The relevant fusion OSCP-GFP-h6 additionally contains a hexahistidine tag at the C-terminus. Expression of OSCP-GFP-h6 in yeast cells lacking endogenous OSCP led to the efficient restoration of growth of cells on the non-fermentable substrate, ethanol. Confocal laser scanning microscopy revealed fluorescence due to GFP in mitochondria of cells expressing OSCP-GFP-h6. Use of immobilised metal ion affinity chromatography enabled the recovery of assembled ATP synthase complexes which contained OSCP-GFP-h6 identified by its mobility on SDS-PAGE and immunoreactivity to anti-OSCP and anti-GFP antibodies. The successful isolation of the assembled multisubunit ATP synthase containing GFP fused to one of the essential subunits of the complex widely expands the potential applications of GFP. In principle, these include the spatial and temporal monitoring of ATP synthase complexes in vivo, and the exploration of interactions involving ATP synthase subunits by fluorescence resonance energy transfer (FRET).
我们已经证明,酵母线粒体ATP合酶的一个亚基OSCP可以作为一种融合蛋白整合到完整的酶中,该融合蛋白是将OSCP在其C末端与维多利亚水母的绿色荧光蛋白(GFP)融合而成。相关的融合蛋白OSCP-GFP-h6在C末端还含有一个六组氨酸标签。在缺乏内源性OSCP的酵母细胞中表达OSCP-GFP-h6能够有效地恢复细胞在非发酵底物乙醇上的生长。共聚焦激光扫描显微镜显示,表达OSCP-GFP-h6的细胞线粒体中存在由GFP产生的荧光。使用固定化金属离子亲和色谱法能够回收组装好的ATP合酶复合物,该复合物含有OSCP-GFP-h6,可通过其在SDS-PAGE上的迁移率以及对抗OSCP和抗GFP抗体的免疫反应性来鉴定。成功分离出含有与复合物必需亚基之一融合的GFP的组装多亚基ATP合酶,极大地扩展了GFP的潜在应用。原则上,这些应用包括在体内对ATP合酶复合物进行空间和时间监测,以及通过荧光共振能量转移(FRET)探索涉及ATP合酶亚基的相互作用。