Identification of conserved residues required for the binding of a tetratricopeptide repeat domain to heat shock protein 90.

摘要: The sequential binding of heat shock protein 90 (hsp90) to a series tetratricopeptide repeat (TPR) proteins is critical its function as molecular chaperone. We have used site-directed mutagenesis clarify the structural basis for hsp90 TPR domain phosphoprotein phosphatase 5 (PP5). This was chosen study because three-dimensional structure known. examined co-immunoprecipitation with wild type and mutant constructs from transfected cells. Only mutations located on one face affected binding. allowed identification groove. Three basic residues that are highly conserved in hsp90-binding extend prominently into this Lys-97 Arg-101 were absolutely required binding, while mutation Arg-74 diminished, but did not abrogate, Mutation Lys-32, another residue groove, also blocked PP5 bound specifically 12-kDa C-terminal fragment hsp90. reduced by acidic fragment. These data suggest conservation, among proteins, groove containing interact near C terminus