Peptidyl-prolyl cis-trans isomerase FKBP1A (F36V mutant) (FKBP1A (F36V))

The Peptidyl-prolyl cis-trans isomerase FKBP1A (F36V mutant), also known as FKBP12 F36V, is an engineered variant of the smallest FKBP family member, which normally catalyzes cis-trans isomerization of proline imidic peptide bonds to accelerate protein folding and modulates receptors like ryanodine receptors (RyRs) and TGFβ type I receptors. The F36V mutation introduces a specificity pocket by truncating phenylalanine-36, allowing remodeled synthetic ligands like AP1903 to bind with sub-nanomolar affinity and over 1,000-fold selectivity versus wild-type FKBP1A, preventing interference from endogenous protein. This mutant is not a natural therapeutic target but a tool for chemical biology and gene therapy, where FKBP1A F36V is fused to signaling domains (e.g., Fas receptor intracellular domain) to enable precise, ligand-induced control of cellular processes like apoptosis. AP1903, a homodimer of the modified ligand, potently triggers cell death in cultured cells and mouse-implanted tumors expressing these fusions, demonstrating in vivo efficacy without affecting unmodified cells. Its role highlights opportunities in cell-based therapies for cancer, though it is confined to genetically modified systems rather than broad disease modulation.

Other names

FKBP12 (F36V mutant)FKBP1A F36VFKBP mutant F36V

Chemical dimerization of FKBP fusion proteins to activate signaling (e.g., apoptosis via Fas receptor fusion), Selective binding to engineered specificity pocket (F36V truncation compensates for ligand modification, enabling >1000-fold selectivity over wild-type)