pH-induced conversion of the transport lectin ERGIC-53 triggers glycoprotein release
pH-induced conversion of the transport lectin ERGIC-53 triggers glycoprotein release
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DOI：
10.1074/jbc.m313245200
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发表时间：
2004-03-26
影响因子：
4.8
通讯作者：
Hauri, HP
中科院分区：
文献类型：
--
作者：
Appenzeller-Herzog, C;Roche, AC;Hauri, HP
再循环甘露糖凝集素ERGIC- 53作为转运受体通过介导一些分泌性糖蛋白的有效内质网（ER）输出而起作用。ER中货物与ERGIC- 53的结合需要Ca 2+。货物释放发生在ERGIC，但分子机制是未知的。在这里，我们报告了纯化的ERGIC- 53在pH 7.4（ER的pH值）下与固定化甘露糖的有效结合，但在稍低的pH值下则不然。当Ca 2+浓度较低时，凝集素的pH敏感性更加突出。一个保守的组氨酸在碳水化合物识别域的中心是凝集素活性所需的，这表明它可能作为一个分子pH/Ca 2+传感器。细胞的酸化抑制ERGIC- 53与已知的货物组织蛋白酶Z相关蛋白的结合，并且ERGIC中这种糖蛋白的解离被细胞器中和所损害，而细胞器中和不损害对照蛋白的转运。结果阐明了可逆凝集素/货物相互作用的分子机制，并建立ERGIC作为分泌途径的最早的低pH位点。
The recycling mannose lectin ERGIC- 53 operates as a transport receptor by mediating efficient endoplasmic reticulum ( ER) export of some secretory glycoproteins. Binding of cargo to ERGIC- 53 in the ER requires Ca2+. Cargo release occurs in the ERGIC, but the molecular mechanism is unknown. Here we report efficient binding of purified ERGIC- 53 to immobilized mannose at pH 7.4, the pH of the ER, but not at slightly lower pH. pH sensitivity of the lectin was more prominent when Ca2+ concentrations were low. A conserved histidine in the center of the carbohydrate recognition domain was required for lectin activity suggesting it may serve as a molecular pH/Ca2+ sensor. Acidification of cells inhibited the association of ERGIC- 53 with the known cargo cathepsin Z- related protein and dissociation of this glycoprotein in the ERGIC was impaired by organelle neutralization that did not impair the transport of a control protein. The results elucidate the molecular mechanism underlying reversible lectin/ cargo interaction and establish the ERGIC as the earliest low pH site of the secretory pathway.