Ellgaard Lars, Frickel Eva-Maria
Institute of Biochemistry, ETH Zurich, CH-8093 Zurich, Switzerland.
Cell Biochem Biophys. 2003;39(3):223-47. doi: 10.1385/CBB:39:3:223.
In eukaryotic cells, the endoplasmic reticulum (ER) plays an essential role in the synthesis and maturation of a variety of important secretory and membrane proteins. For glycoproteins, the ER possesses a dedicated maturation system, which assists folding and ensures the quality of final products before ER release. Essential components of this system include the lectin chaperones calnexin (CNX) and calreticulin (CRT) and their associated co-chaperone ERp57, a glycoprotein specific thiol-disulfide oxidoreductase. The significance of this system is underscored by the fact that CNX and CRT interact with practically all glycoproteins investigated to date, and by the debilitating phenotypes revealed in knockout mice deficient in either gene. Compared to other important chaperone systems, such as the Hsp70s, Hsp90s and GroEL/GroES, the principles whereby this system works at the molecular level are relatively poorly understood. However, recent structural and biochemical data have provided important new insights into this chaperone system and present a solid basis for further mechanistic studies.
在真核细胞中，内质网（ER）在多种重要分泌蛋白和膜蛋白的合成与成熟过程中发挥着关键作用。对于糖蛋白而言，内质网拥有一套专门的成熟系统，该系统有助于蛋白质折叠，并在蛋白质释放到内质网外之前确保最终产物的质量。这个系统的重要组成部分包括凝集素伴侣钙连蛋白（CNX）和钙网蛋白（CRT）以及它们相关的共伴侣蛋白ERp57，一种糖蛋白特异性硫醇-二硫键氧化还原酶。该系统的重要性体现在以下事实：钙连蛋白和钙网蛋白几乎与迄今为止研究的所有糖蛋白相互作用，并且在缺乏任何一个基因的基因敲除小鼠中表现出的衰弱表型也凸显了这一点。与其他重要的伴侣系统，如热休克蛋白70（Hsp70s）、热休克蛋白90（Hsp90s）和GroEL/GroES相比，人们对该系统在分子水平上的工作原理了解相对较少。然而，最近的结构和生化数据为这个伴侣系统提供了重要的新见解，并为进一步的机制研究奠定了坚实的基础。
