HSP-90 AND STEROID RECEPTORS

HSP90是一种普遍存在的热休克蛋白，主要被描述为 关于它对压力的反应和它与类固醇的联系 受体和其他蛋白质。它的功能仍不清楚。长的- 这些研究的术语目标是确定 HSP90。这将通过HSP90的突变图谱来实现 与其他细胞组件相互作用的领域。一系列HSP90 已经准备好了缺失突变体，这些突变体是在无细胞系统中进行的。二 在目标1中将开发更多针对HSP90突变体的新测试。 第一个涉及更一般的HSP90复合体，其中两个与萤火虫有关 荧光素酶复性。突变测试的第三阶段将是 这将包括对HSP90二聚化的测试， ATP的结合和水解，以及HSP90与另一个相关的结合 蛋白质，P59或FKBP59。在目标3中，一系列新的HSP90突变体将 根据从目标1和目标2获得的信息进行准备和测试。 这些突变体将获得精确的缺乏特异性的突变体 在最小的结构变化下的相互作用或作用 分子。这些突变体将被用来描述分开的和 HSP90上相互关联的功能结构域对ITS非常重要 生物活动。

Hsp90 is a ubiquitous heat shock protein that has been described mainly in terms of its response to stress an its association with steroid receptors and other proteins. Its function remains unknown. The long- term objective of these studies is to identify functional elements of hsp90. This will be approached through mutational mapping of hsp90 domains of interaction with other cellular components. A series of hsp90 deletion mutants has been prepared and these in a cell-free system. Two additional novel tests for hsp90 mutants will be developed in Aim 1. The first concerns a more general complex of hsp90 with two involving firefly luciferase renaturation. A third phase of mutant testing will be conducted in Aim 2. This will include tests on hsp90 dimerization, the binding and hydrolysis of ATP, and hsp90 binding to another associated protein, p59 or FKBP59. In Aim 3, a new series of hsp90 mutants will be prepared and tested, based on the information gained from Aims 1 and 2. These mutants will be to obtain precise mutant that lack a specific interaction or function with a minimum of structural alteration in the molecule. These mutants will be used to describe separate and interrelated functional domains on hsp90 that are important to its biological activities.