Co-expression with chaperones can affect protein 3D-structure as exemplified by loss-of-function variants of human prolidase.

Prolidase catalyzes the cleavage of dipeptides containing proline on their C-terminus. The reduction of prolidase activity is the cause of a rare disease named "Prolidase Deficiency". Local structural disorder was indicated as one of the causes for diminished prolidase activity. Previous studies showed that heat shock proteins can partially recover prolidase activity in vivo. To analyze this mechanism of enzymatic activity rescue, we compared the crystal structures of selected prolidase mutants expressed in the absence and in the presence of chaperones. Our results confirm that protein chaperones facilitate the formation of more ordered structures by their substrate protein. These results also suggest that the protein expression system needs to be considered as an important parameter in structural studies.