Orthogonal Signal Tunning : To prevent faults in protein expression

Due to post-translational modifications (PTMs) and/or incorrect folding, synthetic receptors that are intended to act in the secretory pathway frequently fail to perform as planned. Here, synthetic receptors that reside in the cytoplasm, inside the endoplasmic reticulum (ER), or on the plasma membrane were constructed by pivoting the receptor's component pieces and removing any PTMs that were not functioning properly. Rapamycin, abscisic acid, or gibberellin can cause chemically-induced dimerization (CID), which in turn reconstitutes an active protease in the cytoplasmic receptors, which are made up of split-TEVp domains.

The cysteine and asparagine residues, which are typically connected to PTMs, were mutated to make some of these receptors active even though they were inert inside the ER. Finally, orthogonal chemically activated cell-surface receptors were produced by fusing the Notch1 transmembrane domain with the cytoplasmic tTA and extracellular CID domains (OCARs). Cysteine residues in CID domains were changed to create functional OCARs, which allowed mammalian cells to fine-tune orthogonal signaling.

Source:

https://www.nature.com/articles/s41467-022-35161-0

https://www.verywellhealth.com/what-is-a-receptor-on-a-cell-562554