Structural aspects and functional relationships for Hsp90-TPR protein interactions

CAUERHFF AA; GALIGNIANA MD

Frontiers in Structural Biology. Role of molecular chaperones on structural folding, biological functions and drug interactions of client proteins

BENTHAM SCIENCE PUBL LTD

Año: 2018; p. 73 - 173

Nature employs multiple repeat protein scaffolds in order to promoteprotein-protein interactions. In this sense, TPR proteins participate in different naturalpathways, especially in diverse processes of eukaryotic cells. An important aspect forcellular homeostasis is the maintenance of the folding of recently synthesized peptidesas well as all mature proteins such as SHRs. Since, an aberrant protein folding drivesloss of function, this effect induce the expression or modulate the function of molecularchaperones. Hsp90 and Hsp70 with the cooperation of cochaperones are involved in thestabilization of several proteins implicated in signaling, and in the tumor phenotype ofvarious cancers. Therefore, cochaperones are essential component of the cytosolicHsp90 folding pathway, since their function comprises targeting clients to Hsp90,modulating their conformational changes or Hsp90 ATPase activity. The scientificknowledge in the properties and structure of chaperones and the searching ofcompounds that can modulate their function on different cellular mechanism hasbecame remarkably important in the treatment of diverse diseases specially those inwhich a protein mechanism is involved. A description of diverse structural aspects ofHsp90-TPR cochaperones interaction in the context of SHR, as well as a structuralcomparison of different isoforms of Hsp90 is presented in this chapter. Besides, theprimary and new biotechnological approaches inhibiting Hsp90 interactions are alsodiscussed, since Hsp90 and its interactions have become the main targets for inhibitingthe growth of specific tumor types.