Folding and oligomerization of influenza hemagglutinin in the ER and the intermediate compartment.
Folding and oligomerization of influenza hemagglutinin in the ER and the intermediate compartment.
复制标题
内质网和中间室中流感血凝素的折叠和寡聚化。
DOI：
10.1002/j.1460-2075.1995.tb07120.x
复制
发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Helenius,A
中科院分区：
文献类型：
--
作者：
Tatu,U;Hammond,C;Helenius,A
利用流感血凝素（HA）分析了活细胞早期分泌途径中糖蛋白的逐步折叠和寡聚组装。除了成熟三聚体外，还鉴定了六种不同的成熟中间体。其中，所有未完全氧化的形式都位于内质网（ER）中，并与钙连联素（一种膜结合的、类似凝集素的ER伴侣）相关。一旦被完全氧化，透明质酸作为单体从钙连联蛋白中分离出来，迅速抵抗二硫苏糖醇（DTT）的还原。这些广泛折叠的分子的一部分作为单体进入内质网和高尔基复合体之间的中间室。同种三聚体的组装在内质网和中间隔室中发生，而钙连联素没有参与。当分析无锚定的HA分子时，发现它们达到抗DTT的单体构象，但不能三聚体化。综上所述，这些结果提供了透明质酸构象成熟过程中几个中间体的定义和细胞内定位，包括三聚体组装的直接前体。
Influenza hemagglutinin (HA) was used to analyze the stepwise folding and oligomeric assembly of glycoproteins in the early secretory pathway of living cells. In addition to mature trimers, six distinct maturation intermediates were identified. Of these, all the incompletely oxidized forms were located in the endoplasmic reticulum (ER) and associated with calnexin, a membrane‐bound, lectin‐like ER chaperone. Once fully oxidized, the HA dissociated from calnexin as a monomer, which rapidly became resistant to dithiothreitol (DTT) reduction. Part of these extensively folded molecules moved as monomers into the intermediate compartment between the ER and the Golgi complex. Assembly of homotrimers occurred without calnexin‐involvement within the ER and in the intermediate compartment. When anchor‐free HA molecules were analyzed, it was found that they reach the DTT‐resistant monomeric conformation but fail to trimerize. Taken together, the results provide a definition and intracellular localization of several intermediates in the conformational maturation of HA, including the immediate precursor for trimer assembly.