The Polypeptide Binding Conformation of Calreticulin Facilitates Its Cell-surface Expression under Conditions of Endoplasmic Reticulum Stress
The Polypeptide Binding Conformation of Calreticulin Facilitates Its Cell-surface Expression under Conditions of Endoplasmic Reticulum Stress
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DOI：
10.1074/jbc.m110.180877
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发表时间：
2011-01-28
影响因子：
4.8
通讯作者：
Raghavan, Malini
中科院分区：
文献类型：
--
作者：
Jeffery, Elise;Peters, Larry Robert;Raghavan, Malini
我们定义了两类钙网蛋白突变体，它们保留了聚糖结合活性；由于构象效应而表现出增强或降低多肽特异性伴侣活性的分子。在正常情况下，这两组突变体都不会显著影响钙网蛋白介导主要组织相容性复合体I类分子（钙网蛋白底物）组装和运输的能力。然而，在使用thapsigargin处理的细胞中，消耗内质网钙的主要组织相容性复合体I类运输速率随着钙网蛋白的分泌而加速，并且细胞表面钙网蛋白的检测依赖于其多肽结合构象。总之，这些发现确定了钙网蛋白上的一个位点是诱导其多肽结合构象的重要决定因素，并证明了钙网蛋白的多肽结合构象与内质网应激诱导的相互作用的相关性。
We define two classes of calreticulin mutants that retain glycan binding activity; those that display enhanced or reduced polypeptide-specific chaperone activity, due to conformational effects. Under normal conditions, neither set of mutants significantly impacts the ability of calreticulin to mediate assembly and trafficking of major histocompatibility complex class I molecules, which are calreticulin substrates. However, in cells treated with thapsigargin, which depletes endoplasmic reticulum calcium, major histocompatibility complex class I trafficking rates are accelerated coincident with calreticulin secretion, and detection of cell-surface calreticulin is dependent on its polypeptide binding conformations. Together, these findings identify a site on calreticulin that is an important determinant of the induction of its polypeptide binding conformation and demonstrate the relevance of the polypeptide binding conformations of calreticulin to endoplasmic reticulum stress-induced interactions.