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

FEBS Letters

article

Elżbieta Wątor¹  Maria Rutkiewicz¹  Manfred S. Weiss¹  Piotr Wilk¹ 

[1] Macromolecular Crystallography, Helmholtz-Zentrum Berlin für Materialien und Energie

关键词: chaperones;    loss of function;    mutation;    prolidase deficiency;    protein misfolding;    rare diseases;   

DOI  :  10.1002/1873-3468.13877

来源: John Wiley & Sons Ltd.

【 摘 要 】

Prolidase catalyzes the cleavage of dipeptides containing proline on their C terminus. The reduction in 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.

【 授权许可】

Unknown