HSP-90 AND STEROID RECEPTORS

点击翻译按钮获取中文摘要

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.