Hatahet Feras, Ruddock Lloyd W
Biocenter Oulu and Department of Biochemistry, University of Oulu, Finland.
FEBS J. 2007 Oct;274(20):5223-34. doi: 10.1111/j.1742-4658.2007.06058.x. Epub 2007 Sep 24.
Protein folding in the endoplasmic reticulum is often associated with the formation of native disulfide bonds. Their primary function is to stabilize the folded structure of the protein, although disulfide bond formation can also play a regulatory role. Native disulfide bond formation is not trivial, so it is often the rate-limiting step of protein folding both in vivo and in vitro. Complex coordinated systems of molecular chaperones and protein folding catalysts have evolved to help proteins attain their correct folded conformation. This includes a family of enzymes involved in catalyzing thiol-disulfide exchange in the endoplasmic reticulum, the protein disulfide isomerase (PDI) family. There are now 17 reported PDI family members in the endoplasmic reticulum of human cells, but the functional differentiation of these is far from complete. Despite PDI being the first catalyst of protein folding reported, there is much that is still not known about its mechanisms of action. This review will focus on the interactions of the human PDI family members with substrates, including recent research on identifying and characterizing their substrate-binding sites and on determining their natural substrates in vivo.
内质网中的蛋白质折叠通常与天然二硫键的形成有关。其主要功能是稳定蛋白质的折叠结构，尽管二硫键的形成也可以发挥调节作用。天然二硫键的形成并非易事，因此它常常是体内和体外蛋白质折叠的限速步骤。分子伴侣和蛋白质折叠催化剂的复杂协调系统已经进化出来，以帮助蛋白质获得正确的折叠构象。这包括一类在内质网中催化硫醇-二硫键交换的酶，即蛋白质二硫键异构酶（PDI）家族。目前在人类细胞的内质网中已报道有17个PDI家族成员，但它们的功能分化远未完成。尽管PDI是首个被报道的蛋白质折叠催化剂，但其作用机制仍有许多未知之处。本综述将聚焦于人类PDI家族成员与底物的相互作用，包括最近关于鉴定和表征其底物结合位点以及确定其体内天然底物的研究。
