Project Details
Description
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.
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.
Status | Finished |
---|---|
Effective start/end date | 10/1/97 → 8/14/99 |
ASJC
- Applied Microbiology and Biotechnology
- Computers in Earth Sciences
- Instrumentation
- Geochemistry and Petrology
- Medical Laboratory Technology
- Radiation
- Genetics
- Library and Information Sciences
- Molecular Biology
- Structural Biology
- Biophysics
- Biochemistry
- Spectroscopy
- Biotechnology
- History and Philosophy of Science
- Virology
- Inorganic Chemistry
- Cell Biology
- Microbiology