cyclophilinlike

Cyclophilin-like refers to proteins that contain a cyclophilin-like domain (CLD), a member of the peptidyl-prolyl cis-trans isomerase (PPIase) superfamily. Like canonical cyclophilins, cyclophilin-like proteins often catalyze the cis-trans isomerization of proline-containing peptide bonds, aiding in protein folding and conformational maturation. In some members, however, key catalytic residues are altered, and the protein functions as a non-enzymatic chaperone or scaffolding factor rather than an active PPIase.

CLDs are typically about 160–180 amino acids and adopt the conserved cyclophilin structure. Cyclophilin-like proteins can be single-domain proteins or parts of multidomain proteins, with additional regions that determine localization (cytosol, mitochondria, chloroplasts) or mediate interactions (RNA-binding modules, zinc fingers, tetratricopeptide repeats). They occur across bacteria, archaea, and eukaryotes, reflecting broad evolutionary conservation of the PPIase superfamily.

Functional roles span protein folding, stress responses, signaling, and assembly of macromolecular complexes. The best-known example in the broader family is cyclophilin A, which forms a complex with the immunosuppressant cyclosporin A and inhibits calcineurin, modulating immune responses. In other organisms, cyclophilin-like proteins can influence mitochondrial function, RNA processing, or viral replication through direct interactions or regulatory effects.

Taxonomy and nomenclature: the term “cyclophilin-like” emphasizes sequence similarity to cyclophilins rather than strict functional identity. They are distinguished from canonical cyclophilins by variation in the active-site residues and by domain architecture, yet share the characteristic cyclophilin fold.