Insights into peptidyl-prolyl cis-trans isomerase structure and function in immunocytes

Immunol Lett. 2015 Jan;163(1):120-31. doi: 10.1016/j.imlet.2014.11.002. Epub 2014 Nov 13.


Peptidyl-prolyl isomerase (PPIase) catalyzes the interconversion of a specific Pro-imide bond between the cis and trans conformations. Two families of PPIases, cyclophilins and FKBPs, have been extensively studied because of their high affinity for immunosuppressive drugs in particular cyclosporine A and FK506. Despite apparent differences, these protein families share conserved amino acid sequences in their catalytic domains and impose similar enzymatic functions to their substrates. PPIases have been implicated in multiple aspects of cell cycle regulation and cellular processes related to a number of human pathologies, including cancer. More recent studies provide evidence for participation of PPIases in regulation of immune cell functions. In this review, we focus on the role of cyclophilins and FKBPs in the regulation of innate and adaptive immunity functions. PPIase-mediated isomerization of proteins represents a unique signaling mechanism that regulates normal immune functions and contributes to the development of immunopathologies. PPIases may therefore serve as useful diagnostic tools and potential therapeutic targets.

Keywords: CyPA; Cyclosporine A; FK506; FKBP; Immunophilins; PPIases.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Cycle / immunology*
  • Humans
  • Immune System Diseases / diagnosis
  • Immune System Diseases / drug therapy
  • Immune System Diseases / immunology
  • Immune System Diseases / pathology
  • Leukocytes / immunology*
  • Signal Transduction / immunology*
  • Structure-Activity Relationship
  • Tacrolimus Binding Proteins / immunology*


  • FKBP1A protein, human
  • Tacrolimus Binding Proteins