Immunophilins: for the love of proteins

Abstract

Immunophilins are chaperones that may also exhibit peptidylprolyl isomerase (PPIase) activity. This review summarizes our knowledge of the two largest families of immunophilins, namely cyclophilin and FK506-binding protein, and a novel chimeric dual-family immunophilin, named FK506- and cyclosporin-binding protein (FCBP). The larger members of each family are modular in nature, consisting of multiple PPIase and/or protein-protein interaction domains. Despite the apparent difference in their sequence and three-dimensional structure, the three families encode similar enzymatic and biological functions. Recent studies have revealed that many immunophilins possess a chaperone function independent of PPIase activity. Knockout animal studies have confirmed multiple essential roles of immunophilins in physiology and development. An immunophilin is indeed a natural 'protein-philin' (Greek 'philin' = friend) that interacts with proteins to guide their proper folding and assembly.

Master and servant: Regulation of auxin transporters by FKBPs and cyclophilins

“…1). Cyclophilins (also called rotamases and referred to either as Cyps, or ROCs for rotamase Cyps) are named after their high affinity for the cyclic peptide, cyclosporin A [48][49][50], which binds to the core cyclophilin-like domain (see Fig. 1).…”

“…In mammalian immune cells, FK506-FKBP and cyclosporin A-cyclophilin complexes interact with the calcium-dependent serine/threonine protein phosphatase calcineurin, interrupting the phosphorylation signaling pathway and eventually leading to immunosuppression [48]. Rapamycin-bound FKBPs interact with the protein kinase TOR (target of rapamycin) causing cell cycle arrest as well as inducing immunosuppression [52].…”

“…The PPIase activity is inhibited by binding of the corresponding immunosuppressant, but is not directly involved in the immunosuppression mechanisms [53]. In addition, some immunophilins have been demonstrated to possess chaperone or co-chaperone activity that is independent of their PPIase activity and unaffected by immunosuppressant drugs [48,49,54,55]. These are usually larger immunophilins that possess additional structural domains.…”

“…FKBPs and cyclophilins are represented by particularly large families in plants [48,59]. The Arabidopsis genome encodes for 23 FKBP genes compared to Saccharomyces cerevisiae (4), Caenorhabditis elegans (8) and Homo sapiens (15).…”

“…Interaction with the classical chaperone, HSP90, also suggest that TWD1 might function as co-chaperone (reviewed in Refs. [48][49][50]54,59]). Another frequently studied Arabidopsis FKBP protein, PAS-TICCINO (AtFKBP72/PAS1), is involved in the control of cell proliferation and differentiation and was suggested to chaperone the nuclear translocation of a NAC transcription factor [68,69].…”