Stefanovic Sandra, Hegde Ramanujan S
Cell Biology and Metabolism Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Cell. 2007 Mar 23;128(6):1147-59. doi: 10.1016/j.cell.2007.01.036.
Hundreds of proteins are anchored in intracellular membranes by a single transmembrane domain (TMD) close to the C terminus. Although these tail-anchored (TA) proteins serve numerous essential roles in cells, components of their targeting and insertion pathways have long remained elusive. Here we reveal a cytosolic TMD recognition complex (TRC) that targets TA proteins for insertion into the ER membrane. The highly conserved, 40 kDa ATPase subunit of TRC (which we termed TRC40) was identified as Asna-1. TRC40/Asna-1 interacts posttranslationally with TA proteins in a TMD-dependent manner for delivery to a proteinaceous receptor at the ER membrane. Subsequent release from TRC40/Asna-1 and insertion into the membrane depends on ATP hydrolysis. Consequently, an ATPase-deficient mutant of TRC40/Asna-1 dominantly inhibited TA protein insertion selectively without influencing other translocation pathways. Thus, TRC40/Asna-1 represents an integral component of a posttranslational pathway of membrane protein insertion whose targeting is mediated by TRC.
数百种蛋白质通过靠近C端的单个跨膜结构域（TMD）锚定在细胞内膜上。尽管这些尾锚定（TA）蛋白在细胞中发挥着许多重要作用，但其靶向和插入途径的组成部分长期以来一直难以捉摸。在这里，我们揭示了一种胞质TMD识别复合物（TRC），它将TA蛋白靶向插入内质网（ER）膜。TRC中高度保守的40 kDa ATP酶亚基（我们称之为TRC40）被鉴定为Asna-1。TRC40/Asna-1在翻译后以TMD依赖的方式与TA蛋白相互作用，以便递送至ER膜上的蛋白质受体。随后从TRC40/Asna-1释放并插入膜中依赖于ATP水解。因此，TRC40/Asna-1的ATP酶缺陷型突变体选择性地显著抑制TA蛋白插入，而不影响其他转运途径。因此，TRC40/Asna-1代表膜蛋白插入翻译后途径的一个组成部分，其靶向由TRC介导。
