Peptidylproline cis-trans-isomerases: immunophilins

Area of Science:

• Biochemistry
• Molecular Biology
• Cell Biology

Background:

• Peptidylproline cis-trans-isomerase activities (PPIases) are crucial enzymes involved in protein folding and cellular functions.
• PPIases are highly conserved, multifunctional proteins found across diverse cell types and compartments, exhibiting various posttranslational modifications.
• Two main superfamilies, cyclophilins and FKBP (FK506/rapamycin-binding proteins), are defined by their binding to specific immunosuppressants.

Purpose of the Study:

• To review the discovery and diverse functions of PPIases (immunophilins).
• To analyze the roles of immunophilins and their drug complexes in cellular signal-transduction pathways.
• To highlight the impact of PPIase-immunosuppressant interactions on cell viability and function.

Main Methods:

• Literature review of PPIase research.
• Analysis of protein sequences and phylogenetic distribution.
• Examination of posttranslational modifications and cellular localization.
• Investigation of interactions with immunosuppressants (CsA, FK506, rapamycin).

Main Results:

• PPIases regulate protein folding, assembly, trafficking, and act as chaperones.
• Secreted PPIases exhibit inflammatory and chemotactic properties.
• PPIase-immunosuppressant complexes (e.g., CsA, FK506, rapamycin) modulate T-cell signaling and can be toxic.
• Multiple cyclophilin and FKBP genes exist in human DNA, regulating distinct signaling pathways.

Conclusions:

• PPIases (immunophilins) are critical regulators of cellular processes with significant roles in signal transduction.
• The interaction of PPIases with immunosuppressants has profound effects on immune cell function and viability.
• Further research into immunophilins and their complexes offers insights into therapeutic strategies and cellular mechanisms.