STRUCTURE OF PUMILIO NOVEL RNA BINDING DOMAIN

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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.