Prokaryotic and eukaryotic organisms contain proteins related to the major stress inducible protein, hsp70. Whereas E. coli contains a single Hsp70-like gene, eukaryotic organisms, such as Drosophila, contain complex Hsp70 gene families. Some of the constitutively expressed members of this family, termed Heat Shock Cognates (Hscs) are essential for normal growth and their protein products (hscs) are specialized for different subcellular compartments. The proposed experiments are based upon a general model for hsp70- related protein function in which an hsp70-related protein binds stoichiometrically to a protein complex, uses the energy from ATP hydrolysis to alter the complex, and is then released from the complex. The long-term goal of this research is to identify some of the specific protein substrates upon which hsc proteins act and determine both the mechanism and the biological consequences of such action. The proposed experiments will focus on 1) a characterization of the recently isolated Drosophila gene, Hsc3, believed to encode a protein located within the lumen of the endoplasmic reticulum; 2) the purification of the major hsc proteins by ATP-agarose affinity chromatography; 3) the purification of cellular proteins that interact with hsc proteins by affinity chromatography and 4) determining the phenotypes of files carrying mutations in the genes encoding the major hsc proteins, Hsc3 and Hsc4. These studies should identify some of the biological, processes that hsc proteins affect and indicate whether hsc proteins interact with hundreds of proteins or only a small number.
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