GRP94: An HSP90-like protein specialized for protein folding and quality control in the endoplasmic reticulum.

GRP94: An HSP90-like protein specialized for protein folding and quality control in the endoplasmic reticulum.
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DOI:
10.1016/j.bbamcr.2011.10.013
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发表时间:
2012-03
期刊:
Biochimica et biophysica acta
影响因子:
--
通讯作者:
Argon Y
Argon Y
中科院分区:
其他
文献类型:
--
作者:
Marzec M;Eletto D;Argon Y

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葡萄糖调节蛋白94是位于内质网腔内的HSP90样蛋白,因此它是分泌的和膜蛋白的伴侣。它在多细胞生物的发育和生理学中具有重要功能,至少部分原因是这种独特的客户群。GRP94与其他HSP 90蛋白共享许多生化特征,特别是其结构域结构和ATP酶活性,但也显示出独特的活性,如钙结合,这是内质网中条件所必需的。GRP94的作用模式不同于一般的HSP 90主题,在由核苷酸结合诱导的构象变化中,以及在其与辅分子伴侣的相互作用中,辅分子伴侣与已知的胞质辅分子伴侣非常不同。GRP94比许多ER分子伴侣更具选择性,这种选择性的基础仍然不清楚。分子工具和功能测定的最新发展扩大了依赖GRP94活性的客户端的范围,但尚不清楚伴侣蛋白如何结合它们,或者它影响折叠的哪个方面。这些机制问题和其他蛋白质和翻译后修饰差异对GRP94活性的调节提出了新的问题,并提出了未来的研究途径。
Glucose-regulated protein 94 is the HSP90-like protein in the lumen of the endoplasmic reticulum and therefore it chaperones secreted and membrane proteins. It has essential functions in development and physiology of multicellular organisms, at least in part because of this unique clientele. GRP94 shares many biochemical features with other HSP90 proteins, in particular its domain structure and ATPase activity, but also displays distinct activities, such as calcium binding, necessitates by the conditions in the endoplasmic reticulum. GRP94’s mode of action varies from the general HSP90 theme in the conformational changes induced by nucleotide binding, and in its interactions with co-chaperones, which are very different from known cytosolic co-chaperones. GRP94 is more selective than many of the ER chaperones and the basis for this selectivity remain obscure. Recent development of molecular tools and functional assays has expanded the spectrum of clients that rely on GRP94 activity, but it is still not clear how the chaperone binds them, or what aspect of folding it impacts. These mechanistic questions and the regulation of GRP94 activity by other proteins and by post-translational modification differences pose new questions and present future research avenues.
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