Braakman I, Helenius J, Helenius A
Department of Cell Biology, Yale University School of Medicine, New Haven, Connecticut 06510-8002.
Nature. 1992 Mar 19;356(6366):260-2. doi: 10.1038/356260a0.
Being topologically equivalent to the extracellular space, the lumen of the endoplasmic reticulum (ER) provides a unique folding environment for newly synthesized proteins. Unlike other compartments in the cell where folding occurs, the ER is oxidizing and therefore can promote the formation of disulphide bonds. The reducing agent dithiothreitol, when added to living cells, inhibits disulphide formation with profound effects on folding. Taking advantage of this effect, we demonstrate here that folding of influenza haemagglutinin is energy dependent. Metabolic energy is required to support the correct folding and disulphide bond formation in this well characterized viral glycoprotein, to rescue misfolded proteins from disulphide-linked aggregates, and to maintain the oxidized protein in its folded and oligomerization-competent state.
内质网（ER）的管腔在拓扑结构上等同于细胞外空间，为新合成的蛋白质提供了独特的折叠环境。与细胞内发生折叠的其他区室不同，内质网具有氧化性，因此能够促进二硫键的形成。还原剂二硫苏糖醇添加到活细胞中时，会抑制二硫键的形成，对折叠产生深远影响。利用这一效应，我们在此证明流感血凝素的折叠是能量依赖性的。需要代谢能量来支持这种特征明确的病毒糖蛋白的正确折叠和二硫键形成，从二硫键连接的聚集体中拯救错误折叠的蛋白质，并将氧化的蛋白质维持在其折叠且具有寡聚化能力的状态。
