A polypeptide binding conformation of calreticulin is induced by heat shock, calcium depletion, or by deletion of the C-terminal acidic region
A polypeptide binding conformation of calreticulin is induced by heat shock, calcium depletion, or by deletion of the C-terminal acidic region
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DOI：
10.1016/j.molcel.2004.09.001
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发表时间：
2004-09-24
期刊：
影响因子：
16
通讯作者：
Raghavan, M
中科院分区：
文献类型：
--
作者：
Rizvi, SM;Mancino, L;Raghavan, M
人们普遍认为，钙网蛋白的伴侣活性是由其结合含有单糖化低聚糖的糖蛋白的能力所介导的。然而，钙网织蛋白也是一种多肽结合蛋白。在这里，我们发现，热休克、钙耗竭或C末端酸性结构域的缺失会增强纯化的钙网织蛋白与多肽底物的结合，并增强钙网织蛋白的伴侣活性。这些条件也促进了钙网蛋白的寡聚，但寡聚本身并不是增强多肽结合所必需的。在细胞中，钙网蛋白寡聚中间产物在引起蛋白质错误折叠的条件下(热休克和衣霉素处理)和钙耗竭时积累。此外，在细胞中，当显著水平的钙网蛋白寡聚中间产物被诱导时，钙网蛋白与脱糖的主要组织相容性复合体I类重链结合。因此，产生非天然底物的细胞压力条件也会影响钙网蛋白本身的构象性质，并增强其与底物的结合，而不依赖于底物的糖基化。
It is widely believed that the chaperone activity of calreticulin is mediated by its ability to bind glycoproteins containing monoglucosylated oligosaccharides. However, calreticulin is also a polypeptide binding protein. Here we show that heat shock, calcium depletion, or deletion of the C-terminal acidic domain enhance binding of purified calreticulin to polypeptide substrates and enhance calreticulin's chaperone activity. These conditions also enhance calreticulin oligomerization, but oligomerization per se is not required for enhanced polypeptide binding. In cells, calreticulin oligomerization intermediates accumulate in response to conditions that induce protein misfolding (heat shock and tunicamycin treatments), and upon calcium depletion. Additionally, in cells, calreticulin binds to deglycosylated major histocompatibility complex class I heavy chains when significant levels of calreticulin oligomerlzation intermediates are induced. Thus, cell stress conditions that generate nonnative substrates of calreticulin also affect the conformational properties of calreticulin itself, and enhance its binding to substrates, independent of substrate glucosylation.