Abstract

Heat shock proteins (HSPs), also called stress proteins, are a group of proteins that are present in all cells in all life forms. They are induced when a cell undergoes various types of environmental stresses like heat, cold and oxygen deprivation.

HSPs are also present in cells under perfectly normal conditions. They act like 'chaperones,' regulating the folding and the conformational regulation of a variety of signal transduction proteins and cell cycle regulators in the eukaryotic cytosol. To achieve the folding of proteins such as steroid hormone receptors and protein kinases, Hsp90 and Hsp70 cooperate with numerous cofactors containing so-called tetratricopeptide repeat (TPR)1 domains. TPR domains are composed of loosely conserved 34-amino acid sequence motifs that are repeated several times per domain.

The TPR cofactors of the Hsp70/Hsp90 multi-chaperone system interact with the C-terminal domains of Hsp70 and Hsp90. Deletion mutagenesis suggested that the C-terminal sequence motif EEVD-COOH, which is highly conserved in all Hsp70s and Hsp90s, has an important role in TPR-mediated cofactor binding.