Characterization of PROTAC specificity and endogenous protein interactomes using ProtacID

Here we describe ProtacID, a flexible BioID (proximity-dependent biotinylation)-based approach to identify PROTAC-proximal proteins in living cells. ProtacID analysis of VHL- and CRBN-recruiting PROTACs targeting a number of different proteins (localized to chromatin or cellular membranes, and tested across six different human cell lines) demonstrates how this technique can be used to validate PROTAC degradation targets and identify non-productive (i.e. non-degraded) PROTAC-interacting proteins, addressing a critical need in the field of PROTAC development. We also demonstrate that ProtacID can be used to characterize native, endogenous multiprotein complexes without the use of antibodies, or modification of the protein of interest with epitope tags or biotin ligase tagging.

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Publication Details

Journal
Nature Communications
Published
2025-08-29
DOI
https://doi.org/10.1038/s41467-025-63357-7
Citations
2
Primary Topic
Protein Degradation and Inhibitors
Type
article
Field-Weighted Citation Impact
1.61

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article

Characterization of PROTAC specificity and endogenous protein interactomes using ProtacID

C.H. Arrowsmith, Matthew E. R. Maitland, Dalia Baršytė-Lovejoy, Shili Duan et al.
2 citations
Nature Communications
Protein Degradation and Inhibitors
1.61
article

Characterization of PROTAC specificity and endogenous protein interactomes using ProtacID

C.H. Arrowsmith, Matthew E. R. Maitland, Dalia Baršytė-Lovejoy, Shili Duan, Brian Raught, Michael Kanaris, Jonathan St‐Germain, Jing Li, Suman Shrestha, Yan Nie
article en
2 citations

Abstract

Here we describe ProtacID, a flexible BioID (proximity-dependent biotinylation)-based approach to identify PROTAC-proximal proteins in living cells. ProtacID analysis of VHL- and CRBN-recruiting PROTACs targeting a number of different proteins (localized to chromatin or cellular membranes, and tested across six different human cell lines) demonstrates how this technique can be used to validate PROTAC degradation targets and identify non-productive (i.e. non-degraded) PROTAC-interacting proteins, addressing a critical need in the field of PROTAC development. We also demonstrate that ProtacID can be used to characterize native, endogenous multiprotein complexes without the use of antibodies, or modification of the protein of interest with epitope tags or biotin ligase tagging.

Nature CommunicationsVol. 16(1)
University Health Network (CA), University of Toronto (CA), Princess Margaret Cancer Centre (CA), Structural Genomics Consortium (CA)
Bristol-Myers Squibb, Pfizer, Bayer, McGill University, Genome Canada, Merck KGaA, Ontario Genomics, European Federation of Pharmaceutical Industries and Associations, Ontario Genomics Institute, University of Toronto, Mitacs, Genentech, Canadian Institutes of Health Research
Openalex Percentile: Top 15%
Protein Degradation and Inhibitors
1.61
DOIOpen Access PDFOpenAlex
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