An unstructured C-terminal region of the Hsp90 Co-chaperone p23 is important for its chaperone function

p23 is a co-chaperone of the heat shock protein Hsp90. p23 binds to Hsp90 i n its ATP-bound state and, on its own, interacts specifically with non-nati ve proteins. In our attempt to correlate these functions to specific region s of p23 we have identified an unstructured region in p23 that maps to the C-terminal part of the protein sequence. This unstructured region is dispen sible for interaction of p23 with Hsp90, since truncated p23 can still form complexes with Hsp90. in contrast, however, truncation of the C-terminal 3 0 amino acid residues of p23 affects the ability of p23 to bind non-native proteins and to prevent their non-specific aggregation. The isolated C-term inal region itself is not able to act as a chaperone nor is it possible to complement truncated p23 by addition of this peptide. These results imply t hat the binding site for Hsp90 is contained in the folded domain of p23 and that for efficient interaction of p23 with non-native proteins both the fo lded domain and the C-terminal unstructured region are required. (C) 1999 A cademic Press.