Role of Peptidyl-Prolyl-cis/trans-Isomerases in Pathologic Processes

Enzymes grouped into a superfamily of peptidyl-prolyl-cis/trans-isomerases (PPIases) possess chaperone activity and fold proteins into active configuration by catalyzing slow cis/trans isomerization on proline-peptide bonds. PPIases are conservative and abundant among Pro- and Eukaryotes. Many proteins involved in disease processes require modification; thus, PPIases can play an important role in pathogenesis. Analysis of the experimental data published so far allows us to classify the involvement of PPIases in pathologic process as follows: (1) Modification of outer membrane porines and channels, components of secretion systems, and secreted proteins by FkpA-like and SurA-like PPIases. Such modification helps to avoid or suppress host cell immune response; (2) Use of host PPIases (like ROC1 of Arabidopsis thaliana) for modification of effector proteins necessary for pathogenesis. Bacterial protein surA participates in suppression of host immune reaction and can be recognized as elicitor of immune response in other host. SurA is essential for formation of bacterial flagella and pile. We suggest that SurA protein can be involved in activation of some effector proteins, while other effectors, for their activation in host cell, may need PPIases of ROC1-type. Viruses and some other obligate parasites use host PPIases for their own protein modification as an essential step for the pathogen multiplication. In this case modified host PPIases are capable to suppress the pathogenesis. That makes the PPIases potential targets for gene therapy.