This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The abundant cytoplasmic molecular chaperone Hsp90 and its co-chaperones are critical for the activity of steroid receptors, oncogenic tyrosine kinases and additional diverse proteins involved in signaling pathways and cell cycle control. Hsp90 and co-chaperones interact in an ATP-dependent pathway that facilitates the folding of substrate proteins to their native state. Hsp90 inhibitors have been shown to slow the ability of Candida albicans to develop drug resistance. A focus of our work is to characterize the interaction of Hsp90 with yeast-specific proteins, first in S. cerevisiae and then in C. albicans. We developed an assay that allows us to isolate native yeast Hsp90 complexes that contain both known co-chaperone proteins and novel presumed client proteins. Using peptide mass mapping we identified four novel Hsp90 interacting proteins and confirmed another interaction. In our efforts to determine how Hsp90 interacts with diverse client proteins, we will examine the interaction of Hsp90 and co-chaperones with these and other proteins in order to develop a more comprehensive picture of the in vivo mechanisms of the Hsp90 molecular machine.
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