A conserved 'hydrophobic staple motif' plays a crucial role in the refolding of human glutathione transferase Pl-l

A hydrophobic staple motif is strictly conserved in the core of all soluble glutathione transferases (GSTs) as well as in other protein structures. The role of this local interaction in folding and stability of human GSTP1-1 has been analysed by site directed mutagenesis. The results show that the hydrophobic staple motif, by restricting the number of conformations of the alpha6-helix relative to the alpha1-helix, favours the formation of essential interdomain contacts and thereby accelerate the folding process. We suggest that the strict conservation of the hydrophobic staple motif reflect an evolutionary pressure for proteins to fold rapidly. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.