The 90 kilodalton heat shock protein (hsp90) is a highly abundant, highly conserved protein in both prokaryotes and eukaryotes. In certain mammalian cell types, the isozymes of hsp90 can comprise as much as 2% of total cellular protein under nonstess conditions. At elevated temperatures, both the transcription and translation of hsp90 increase dramatically suggesting that it plays a major role in the heat shock response. In fact, like several other heat shock proteins, hsp90 has been shown to chaperone protein folding in vitro; that is, addition of hsp90 prevents nonproductive aggregation of protein molecules during refolding reactions. In addition, hsp90 has been shown to modulate the activities of a variety of signal transduction molecules including steroid hormone receptors (such as the glucocorticoid and estrogen receptors) as well as nonreceptor tyrosine kinases (such as v-src). Finally, hsp90 has been found to be associated with molecules such as calmodulin, actin, tubulin and serine/threonine kinases such as casein kinase II and eIF-2a kinase. Overall, the studies of the interactions between hsp90 and these various signal transduction molecules hint that the mechanism through which hsp90 modulates the activities of these molecules and its role as a chaperone may overlap; these signaling molecules may have co-opted the ability of hsp90 to stabilize folding intermediates into regulating conformational changes necessary for signaling. Therefore, to begin probing these mechanisms, we have initiated a structural study of htpG (high temperature production protein G), the Escherichia coli member of the hsp90 family.

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR001646-19
Application #
6491092
Study Section
Project Start
2001-08-15
Project End
2002-08-14
Budget Start
Budget End
Support Year
19
Fiscal Year
2001
Total Cost
$142,703
Indirect Cost
Name
Cornell University
Department
Type
DUNS #
City
Ithaca
State
NY
Country
United States
Zip Code
14850
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