Nature employs multiple repeat protein scaffolds in order to promote
protein-protein interactions. In this sense, TPR proteins participate in different natural
pathways, especially in diverse processes of eukaryotic cells. An important aspect for
cellular homeostasis is the maintenance of the folding of recently synthesized peptides
as well as all mature proteins such as SHRs. Since, an aberrant protein folding drives
loss of function, this effect induce the expression or modulate the function of molecular
chaperones. Hsp90 and Hsp70 with the cooperation of cochaperones are involved in the
stabilization of several proteins implicated in signaling, and in the tumor phenotype of
various cancers. Therefore, cochaperones are essential component of the cytosolic
Hsp90 folding pathway, since their function comprises targeting clients to Hsp90,
modulating their conformational changes or Hsp90 ATPase activity. The scientific
knowledge in the properties and structure of chaperones and the searching of
compounds that can modulate their function on different cellular mechanism has
became remarkably important in the treatment of diverse diseases specially those in
which a protein mechanism is involved. A description of diverse structural aspects of
Hsp90-TPR cochaperones interaction in the context of SHR, as well as a structural
comparison of different isoforms of Hsp90 is presented in this chapter. Besides, the
primary and new biotechnological approaches inhibiting Hsp90 interactions are also
discussed, since Hsp90 and its interactions have become the main targets for inhibiting
the growth of specific tumor types.
Keywords: TPR domain, TPR protein structure, Hsp90-TPR protein interaction,
Hsp90 cochaperones, Protein folding, Steroid hormone receptor, Hsp90 inhibitors.
