Calcineurin A-cyclophilin B complex (CNA-CypB)

Calcineurin A (PPP3CA) is a calcium- and calmodulin-dependent serine/threonine protein phosphatase that plays a pivotal role in the activation of T-lymphocytes by dephosphorylating the Nuclear Factor of Activated T-cells (NFAT) [2, 4]. Cyclophilin B (PPIB) is a member of the immunophilin family with peptidyl-prolyl cis-trans isomerase activity, primarily located within the endoplasmic reticulum but also found in the cytosol and extracellular space [1, 3]. The Calcineurin A-cyclophilin B complex refers to the inhibitory assembly formed when the drug Cyclosporine A binds to Cyclophilin B, which then physically associates with Calcineurin A to block its enzymatic site [4, 6]. This interaction prevents NFAT from entering the nucleus, thereby suppressing the transcription of pro-inflammatory cytokines like interleukin-2 (IL-2) [4]. This target complex is a mediator of the immunosuppressive effects of Cyclosporine A, used extensively to prevent organ transplant rejection and treat autoimmune conditions such as rheumatoid arthritis and psoriasis [5]. Additionally, the complex and its components are involved in the life cycles of certain viruses, including Hepatitis C, where cyclophilins act as essential host factors for viral replication [1].

Other names

PPP3CA-PPIB complexCalcineurin-PPIB complexCyclosporine-Cyclophilin B-Calcineurin complexProtein phosphatase 3 catalytic subunit alpha-peptidyl-prolyl cis-trans isomerase B complex

Inhibition of Calcineurin phosphatase activity through the formation of a ternary drug-immunophilin-phosphatase complex