STRUCTURE OF PUMILIO NOVEL RNA BINDING DOMAIN

PUMILIO 新型 RNA 结合域的结构

• 批准号: 6339104
• 负责人: ANEEL K. AGGARWAL
• 金额: $ 2.33万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-08-15 至 2001-08-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6339104
• 关键词: bioimaging /biomedical imaging; biological products; biomedical resource; proteins; radiography; structural biology

The 90 kilodalton heat shock protein (hsp90) is a highly abundant, highly conserved protein in both prokaryotes and eukaryotes. In certain mammalian cell types, the isozymes of hsp90 can comprise as much as 2% of total cellular protein under nonstess conditions. At elevated temperatures, both the transcription and translation of hsp90 increase dramatically suggesting that it plays a major role in the heat shock response. In fact, like several other heat shock proteins, hsp90 has been shown to chaperone protein folding in vitro; that is, addition of hsp90 prevents nonproductive aggregation of protein molecules during refolding reactions. In addition, hsp90 has been shown to modulate the activities of a variety of signal transduction molecules including steroid hormone receptors (such as the glucocorticoid and estrogen receptors) as well as nonreceptor tyrosine kinases (such as v-src). Finally, hsp90 has been found to be associated with molecules such as calmodulin, actin, tubulin and serine/threonine kinases such as casein kinase II and eIF-2a kinase. Overall, the studies of the interactions between hsp90 and these various signal transduction molecules hint that the mechanism through which hsp90 modulates the activities of these molecules and its role as a chaperone may overlap; these signaling molecules may have co-opted the ability of hsp90 to stabilize folding intermediates into regulating conformational changes necessary for signaling. Therefore, to begin probing these mechanisms, we have initiated a structural study of htpG (high temperature production protein G), the Escherichia coli member of the hsp90 family.

90kodalton热休克蛋白(HSP90)是一种高度丰富的， 原核生物和真核生物中高度保守的蛋白质。在……里面 某些哺乳动物细胞类型，HSP90的同工酶可以包括 在非静止条件下，相当于细胞总蛋白的2%。在… 温度升高，HSP90的转录和翻译 戏剧性的增加表明它在 热休克反应。事实上，和其他几种热休克蛋白一样， HSP90已被证明在体外可以折叠伴侣蛋白；也就是说， 添加HSP90可防止蛋白质的非生产性聚集 分子在重折叠反应中。此外，HSP90已经被 被证明可以调节各种信号转导的活动 包括类固醇激素受体的分子(如 糖皮质激素和雌激素受体)以及非受体酪氨酸 激酶(如v-src)。最后，HSP90被发现是 与钙调蛋白、肌动蛋白、微管蛋白和 丝氨酸/苏氨酸激酶，如酪蛋白激酶II和eIF-2a激酶。 总体而言，热休克蛋白90与这些基因相互作用的研究 不同的信号转导分子暗示，通过 哪些HSP90调节这些分子的活性及其作用 作为伴侣可能会重叠；这些信号分子可能有 利用HSP90稳定折叠中间体的能力 调控信号传递所需的构象变化。因此， 为了开始探索这些机制，我们已经启动了一个结构性的 大肠杆菌高温生产蛋白G(HtpG)的研究 Coli是HSP90家族的成员。