HSP 90 ASSOCIATION WITH STEROID RECEPTORS AND PROTEINS

热休克蛋白90是一种普遍存在的热休克蛋白，是一种主要的细胞质分子 监护人它已被描述主要是关于其协会 类固醇受体和其他一些调节蛋白 帮助它们折叠成原生状态。其主要目标是 建议是描述多蛋白伴侣途径， hsp 90及其辅助分子伴侣的作用机制。三 提出了具体目标。在目标1中，我们将继续开发和 研究hsp 70和hsp 90依赖的分子伴侣系统用于复性 变性蛋白质。该系统至少涉及以下方面的合作： 四种蛋白质和一个最佳的系统可能会包括一些额外的 proteins.这些蛋白质的单独和合作功能将 然后详细检查。在目标2中，我们将继续描述 HSP 90的结构和功能域。重点将放在 核苷酸结合结构域在热休克蛋白90活性中的重要性以及 描述与蛋白质底物和蛋白质底物相互作用的结构域。 共同伴侣，p23。我们的主要方法将是描述一个 多种多样的hsp 90突变体。一种新的热休克蛋白90同源物，TRAP-1， 研究目的3这种蛋白质的几个基本特性必须首先 介绍了然后将其与hsp 90以各种方式进行比较。这 将提供新的信息，蛋白质的一般特点， hsp 90家族，并应揭示TRAP-1是否具有非常独特的功能 与HSP 90重叠的基因这些研究将提供重要的新信息。 关于细胞质伴侣的一般信息加上一个更清晰的 HSP 90的功能定义。

hsp90 is a ubiquitous heat shock protein and a major cytoplasmic molecular chaperone. It has been described mainly in relation to its association with steroid receptors and some other regulatory proteins where it appears to assist in their folding to a native state. The main objectives of this proposal are to describe the multi-protein chaperoning pathway involving hsp90 and the mechanisms of action of hsp90 and its co-chaperones. Three specific aims are proposed. In Aim 1, we will continue to develop and study an hsp70 and hsp90 dependent chaperoning system for the renaturation of denatured proteins. This system involves the cooperation of at least four proteins and an optimal system will probably include a few additional proteins. The individual and cooperative functions of these proteins will then be examine din detail. In Aim 2, we will continue to describe the structural and functional domains of hsp90. Emphasis will be on the importance of the nucleotide binding domain in hsp90 activity and the descriptions of domains that interact with protein substrates and with the co-chaperone, p23. Our main approach will be the characterization of a wide variety of hsp90 mutants. A novel hsp90 homolog, TRAP-1, will be studied in Aim 3. Several basic properties of this protein must first be described. It will then be compared with hsp90 in a variety of ways. This will provide new information on the general features of proteins in the hsp90 family and should reveal whether TRAP-1 has very distinct functions that overlap with hsp90. These studies should provide important nw information on cytoplasmic chaperoning in general plus a much clearer definition of the functions of hsp90.