Udenfriend S, Kodukula K
Roche Institute of Molecular Biology, Roche Research Center, Nutley, New Jersey 07110, USA.
Annu Rev Biochem. 1995;64:563-91. doi: 10.1146/annurev.bi.64.070195.003023.
Glycosylphosphatidylinositol (GPI) linkage is a fairly common means of anchoring membrane proteins to eukaryotic cells, although the exact function of the GPI linkage is not clear. The nascent form of a typical GPI protein contains a hydrophobic NH2-terminal signal peptide that directs it to the ER. There the signal peptide is removed by NH2-terminal signal peptidase. Nascent forms of GPI-linked proteins contain a second hydrophobic peptide at their COOH terminus. The COOH-terminal peptide is also removed during processing and the GPI moiety is ultimately linked to what had been an internal sequence in the nascent protein. Two independent pathways are involved in the biosynthesis of GPI proteins, GPI formation, and processing of the nascent protein with attachment of the GPI moiety. Studies in whole cells and in cell-free systems indicate that structural requirements around the COOH-terminal cleavage site of nascent proteins are similar to those at the cleavage site of NH2-terminal signal peptidase. However, COOH-terminal processing requires a transmidase for which evidence is presented as well as a proposed mechanism of its action.
糖基磷脂酰肌醇（GPI）连接是将膜蛋白锚定到真核细胞的一种相当常见的方式，尽管GPI连接的确切功能尚不清楚。典型GPI蛋白的新生形式含有一个疏水性的NH2末端信号肽，该信号肽将其导向内质网。在那里，信号肽被NH2末端信号肽酶切除。GPI连接蛋白的新生形式在其COOH末端含有第二个疏水性肽段。COOH末端肽段在加工过程中也会被去除，GPI部分最终与新生蛋白中的一个内部序列相连。GPI蛋白的生物合成、GPI的形成以及新生蛋白与GPI部分连接的加工过程涉及两条独立的途径。在全细胞和无细胞系统中的研究表明，新生蛋白COOH末端切割位点周围的结构要求与NH2末端信号肽酶切割位点的结构要求相似。然而，COOH末端加工需要一种转酰胺酶，文中给出了相关证据以及其作用的一种推测机制。
