A Constrained Degron Tag Engineered to Enhance Auxin-Inducible Protein Degradation.

ACS Synth Biol 2026

Han Z, Alkhadrawi A, Tofani S, Zhang W, Chi LA et al.

Abstract

The auxin-inducible degron (AID) system enables targeted protein degradation in vivo. Conventionally, the AID tag is fused directly to the terminus of the target protein; however, its intrinsically disordered nature and destabilizing motifs can render it susceptible to premature proteolytic removal from its tagged protein, resulting in incomplete degradation upon auxin induction. In addition, direct terminal fusion of the conventional AID tag may compromise protein stability. To address these limitations, we introduce a new degron design in which the conventional AID tag, mIAA7, is inserted into an exposed loop of green fluorescent protein (GFP). The resulting engineered GFP variant, termed the “constrained AID” (cAID) tag, was validated in the industrially important oleaginous yeast

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