Linker-Length Landscape Mapping Enables Coupling of Diverse Synthetic Chemically Induced Dimerization Systems to Molecular Readouts
Published in bioRxiv (Preprint), 2026
Pan Y, Kang S, **Nakajima An D**, Yu Y, DiMaio F, Gu L. Linker-Length Landscape Mapping Enables Coupling of Diverse Synthetic Chemically Induced Dimerization Systems to Molecular Readouts. bioRxiv; 2026. doi: https://doi.org/10.64898/2026.07.01.735888 https://www.biorxiv.org/content/10.64898/2026.07.01.735888v1
We introduce a strategy for coupling synthetic chemically induced dimerization (CID) systems to functional readouts by engineering the linker-mediated coupling interface. Using single-fluorescent-protein sensors built around circularly permuted GFP, we mapped how paired N- and C-terminal linker lengths determine CID-to-output coupling across nanobody-, monobody-, and de novo-designed CID architectures, yielding sensors with dynamic ranges up to 1270% and robust responses in mammalian cells.
Read our preprint here: https://www.biorxiv.org/content/10.64898/2026.07.01.735888v1
