Peptidyl-prolyl cis-trans isomerase FKBP1A–Centrosomal protein of 250 kDa ternary complex (FKBP12–CEP250 complex)

The FKBP12–CEP250 ternary complex is a chemically induced protein-protein interaction formed by the recruitment of the cytosolic chaperone FKBP12 (Peptidyl-prolyl cis-trans isomerase FKBP1A) to the centrosomal protein 250 (CEP250, also known as C-Nap1) via a molecular glue (PNAS, 2020; NIH.gov). This interaction was first characterized using the natural product WDB002, which binds to the topologically flat coiled-coil domain of CEP250, a surface previously considered undruggable by conventional small molecules (ResearchGate, 2020). Biologically, the formation of this complex disrupts the normal function of CEP250 in maintaining centrosome cohesion, thereby interfering with NEK2-mediated centrosome separation during the cell cycle (Arxiv.org, 2025). This mechanism has therapeutic potential in oncology, where centrosome disruption can lead to cell cycle arrest or apoptosis in cancer cells (Revmed.com, 2020). Additionally, the complex has been explored for antiviral applications, as CEP250 is a known host interactor for the SARS-CoV-2 Nsp13 protein (RCSB.org, 2020). The discovery of this complex highlights the genetically programmable nature of FKBP12-mediated recognition, allowing small molecules to reprogram the chaperone to target diverse, previously inaccessible proteins (PNAS, 2020).

Other names

FKBP12–C-Nap1 complexFKBP12–CEP250–WDB002 complexFKBP1A–CEP250 complexFKBP12–CEP250 ternary complex

Molecular glue-induced proximity leading to disruption of centrosome cohesion and inhibition of NEK2-mediated centrosome separation