Summary

The blueprint for the molecules required for life are stored in genes. At any given time, only a subset of the genes in a cell are expressed while the others remain dormant. It is this regulation of gene expression that allows a bacterial cell to respond to changes in the environment and also defines how a single fertilized cell will develop into an adult human. For several years, the factors that mediate gene regulation remained elusize but now we know that they are proteins with the capacity to bind DNA. The Heat Shock Factor from Kluyveromyces lactis is one of these DNA binding proteins. This protein evolved to mediate a rapid response to increased heat that results in the upregulation of heat shock proteins capable of protecting other cellular proteins from misfolding. Heat Shock Factor accomplishes the upregulation of gene expression by binding DNA through its conserved "winged" helix-turn-helix domain and recruiting the transcriptional machinery with a transactivation domain. Heat Shock Factor has been shown to bind DNA optimally as a trimer unlike other helix-turn-helix proteins which bind DNA as dimers. The structure of the "winged" helix-turn-helix domain of Heat Shock Factor has been solved and reveals several novel protein-protein interaction domains which mediate trimerization of the protein. Also, Heat Shock Factor makes only minimal contacts with DNA and these protein-DNA interactions appear to be favored at higher temperatures. The sequence of both the "winged" helix-turn-helix domain and the trimerization domain has changed very little over evolutionary time and in extant species the sequence similarity appears to correlate well with functional similarity. The Heat Shock Factor is a critical component of the cells response to environmental stress and during hyperthermia in mammals it has been shown that the heat shock response plays an important neuro-protective role.