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bioRxiv · 10.1101/2024.07.18.603056

Induced degradation of SNAP-fusion proteins

Abraham Pol, S.·Liljenberg, S.·Barr, J.·Simon, G.·Wong-Dilworth, L.·Paterson, D. L.·Berishvili, V. P.·Bottanelli, F.·Kaschani, F.·Kaiser, M.·Pettersson, M.·Hellerschmied, D.
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Abstract

Self-labeling protein tags are an efficient means to visualize, manipulate, and isolate engineered fusion proteins with suitable chemical probes. The SNAP-tag, which covalently conjugates to benzyl-guanine and -chloropyrimidine derivatives is used extensively in fluorescence microscopy, given the availability of suitable SNAP-ligand-based probes. Here, we extend the applicability of the SNAP-tag to targeted protein degradation. We developed a set of SNAP PROteolysis TArgeting Chimeras (SNAP-PROTACs), which recruit the VHL or CRBN-ubiquitin E3 ligases to induce the degradation of SNAP-fusion proteins. Endogenous tagging enabled the visualization and the selective depletion of a SNAP-clathrin light chain fusion protein using SNAP-PROTACs. The addition of PROTACs to the SNAP-tag reagent toolbox facilitates the comprehensive analysis of protein function with a single gene tagging event.

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Abraham Pol, S., Liljenberg, S., Barr, J., Simon, G., Wong-Dilworth, L., Paterson, D. L., Berishvili, V. P., Bottanelli, F., Kaschani, F., Kaiser, M., Pettersson, M., Hellerschmied, D.. 2024-07-18. Induced degradation of SNAP-fusion proteins. https://doi.org/10.1101/2024.07.18.603056

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