Boca-dependent maturation of β-propeller/EGF modules in low-density lipoprotein receptor proteins
Boca-dependent maturation of β-propeller/EGF modules in low-density lipoprotein receptor proteins
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DOI：
10.1038/sj.emboj.7600132
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发表时间：
2004-03-24
期刊：
影响因子：
11.4
通讯作者：
Mann, RS
中科院分区：
文献类型：
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作者：
Culi, J;Springer, TA;Mann, RS
细胞表面受体蛋白的胞外部分通常由独立折叠的蛋白质结构域组成。当它们被翻译到内质网（ER）中时，这些结构域中的一些需要蛋白伴侣来帮助它们折叠。低密度脂蛋白受体（LDLR）家族的成员需要在果蝇中称为博卡的分子伴侣，或在小鼠中称为中胚层发育的直系同源物。所有LDLR都有至少一个六叶β螺旋桨结构域，紧接着是表皮生长因子（EGF）重复序列。我们在这里表明，博卡是特别需要的成熟，这些β-螺旋桨/EGF模块通过分泌途径，但不需要其他LDLR域。蛋白质相互作用数据表明，随着LDLR被翻译到ER中，博卡与P-螺旋桨结合。随后，一旦EGF重复序列被翻译，β-螺旋桨/EGF模块达到对博卡具有较低亲和力的更成熟状态。我们还表明，博卡依赖β螺旋桨/EGF模块不仅在整个LDLR家族中发现，而且在哺乳动物EGF配体的前体中也发现。
The extracellular portions of cell surface receptor proteins are often comprised of independently folding protein domains. As they are translated into the endoplasmic reticulum (ER), some of these domains require protein chaperones to assist in their folding. Members of the low-density lipoprotein receptor (LDLR) family require the chaperone called Boca in Drosophila or its ortholog, Mesoderm development, in the mouse. All LDLRs have at least one six-bladed beta-propeller domain, which is immediately followed by an epidermal growth factor (EGF) repeat. We show here that Boca is specifically required for the maturation of these beta-propeller/EGF modules through the secretory pathway, but is not required for other LDLR domains. Protein interaction data suggest that as LDLRs are translated into the ER, Boca binds to the P-propeller. Subsequently, once the EGF repeat is translated, the beta-propeller/EGF module achieves a more mature state that has lower affinity for Boca. We also show that Boca-dependent beta-propeller/EGF modules are found not only throughout the LDLR family but also in the precursor to the mammalian EGF ligand.