20.500.12556/RUL-164775 Designed allosteric protein logic The regulation of protein function by external or internal signals is one of the key features of living organisms. The ability to directly control the function of a selected protein would represent a valuable tool for regulating biological processes. Here, we present a generally applicable regulation of proteins called INSRTR, based on inserting a peptide into a loop of a target protein that retains its function. We demonstrate the versatility and robustness of coiled-coil-mediated regulation, which enables designs for either inactivation or activation of selected protein functions, and implementation of two-input logic functions with rapid response in mammalian cells. The selection of insertion positions in tested proteins was facilitated by using a predictive machine learning model. We showcase the robustness of the INSRTR strategy on proteins with diverse folds and biological functions, including enzymes, signaling mediators, DNA binders, transcriptional regulators, reporters, and antibody domains implemented as chimeric antigen receptors in T cells. Our findings highlight the potential of INSRTR as a powerful tool for precise control of protein function, advancing our understanding of biological processes and developing biotechnological and therapeutic interventions. cell signalling protein folding biokemija beljakovine proteini DNK receptorji protitelesa true false true Angleški jezik Slovenski jezik Članek v reviji 2024-11-11 14:44:57 2024-11-11 14:44:57 2024-11-22 14:56:05 0000-00-00 00:00:00 2024 0 0 15 str. art. 8 Vol. 10 2024 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 577 2056-5968 10.1038/s41421-023-00635-y 183898371 s41421-023-00635-y_(1).pdf s41421-023-00635-y_(1).pdf 1 6E2EA33A3363AE51623FDF5EA116200E 924dd28daa197f853da2d28f4b6b5451b43374eb7b303914d6cba11c4112354c fd4536b7-a032-11ef-b232-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=195449 https://www.nature.com/articles/s41421-023-00635-y 1 c8bd7425-a032-11ef-b232-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=195448 Medicinska fakulteta 0 0 0