STRUCTURAL CHARACTERIZATION OF ESCHERICHIA COLI HSP90 HOMOLOGUE

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.