HSP 90 ASSOCIATION WITH STEROID RECEPTORS AND PROTEINS

HSP90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。对它的描述主要是与它的联系有关的 与类固醇受体和其他一些调节蛋白结合在一起 以帮助它们折叠成原生状态。这次会议的主要目标是 建议描述涉及到的多蛋白伴侣途径 HSP90及其辅助伴侣的作用机制。三 提出了具体的目标。在目标1中，我们将继续发展和 依赖HSP70和HSP90的伴侣系统用于复性的研究 变性蛋白质。这一系统至少涉及到 四种蛋白质和一个最佳系统可能会包括几个额外的 蛋白质。这些蛋白质的个体和协作功能将 然后对DIN进行详细检查。在目标2中，我们将继续描述 HSP90的结构和功能结构域。重点将放在 核苷酸结合域在热休克蛋白90活性中的重要性 描述与蛋白质底物相互作用的结构域以及与 共同监护人，第23页。我们的主要方法将是描述一个 HSP90突变体种类繁多。一个新的HSP90同源物，TRAP-1，将是 在目标3中研究。这种蛋白质的几个基本性质必须首先 描述。然后将它与HSP90以各种方式进行比较。这 将提供有关蛋白质的一般特征的新信息 HSP90家族，应该揭示TRAP-1是否具有非常独特的功能 这与HSP90重叠。这些研究应该提供重要的西北地区 关于细胞质伴侣的一般信息加上一个更清楚的 HSP90功能的定义。

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.