STRUCTURE OF PUMILIO NOVEL RNA BINDING DOMAIN

PUMILIO 新型 RNA 结合域的结构

• 批准号: 6667769
• 负责人: ANEEL K. AGGARWAL
• 金额: $ 14.27万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-30 至 2003-08-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6667769
• 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.

90千道尔顿热休克蛋白（hsp 90）是一种高度丰富的， 在原核生物和真核生物中高度保守的蛋白质。 在 在某些哺乳动物细胞类型中，hsp 90的同工酶可包含如 在非应激条件下约占细胞总蛋白的2%。 在 升高的温度，热休克蛋白90的转录和翻译 这表明它在人类的进化中起着重要作用。 热休克反应 事实上，和其他几种热休克蛋白一样， HSP 90已显示在体外陪伴蛋白质折叠;即， 加入HSP 90可防止蛋白质的非生产性聚集 再折叠反应期间的分子。 此外，HSP 90已被 显示调节多种信号转导的活性 包括类固醇激素受体的分子（例如 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，HSP 90被发现是 与分子如钙调蛋白、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。 总的来说，研究HSP 90与这些细胞之间的相互作用， 各种信号转导分子暗示， 热休克蛋白90调节这些分子的活性及其作用 因为分子伴侣可能重叠;这些信号分子可能具有 利用热休克蛋白90稳定折叠中间体的能力 调节信号传导所必需的构象变化。 因此，我们认为， 为了开始探索这些机制，我们启动了一个结构性的 htpG（高温生产蛋白G）的研究， 大肠杆菌HSP 90家族成员。