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Repurposing an endogenous degradation domain for antibody-mediated disposal of cell-surface proteins

The exquisite specificity of antibodies can be harnessed to effect targeted degradation of membrane proteins. Here, we demonstrate targeted protein removal utilising a protein degradation domain derived from the endogenous human protein Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9). Recombin...

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Bibliographic Details
Main Authors: Schmitt, Janika (Author) , Poole, Emma (Author) , Groves, Ian (Author) , Owen, David J. (Author) , Graham, Stephen C. (Author) , Sinclair, John (Author) , Kelly, Bernard T. (Author)
Format: Article (Journal)
Language:English
Published: 29 January 2024
In: EMBO reports
Year: 2024, Volume: 25, Issue: 3, Pages: 951-970
ISSN:1469-3178
DOI:10.1038/s44319-024-00063-3
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s44319-024-00063-3
Verlag, kostenfrei, Volltext: https://www.embopress.org/doi/full/10.1038/s44319-024-00063-3
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Author Notes:Janika Schmitt, Emma Poole, Ian Groves, David J Owen, Stephen C Graham, John Sinclair & Bernard T Kelly
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Summary:The exquisite specificity of antibodies can be harnessed to effect targeted degradation of membrane proteins. Here, we demonstrate targeted protein removal utilising a protein degradation domain derived from the endogenous human protein Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9). Recombinant antibodies genetically fused to this domain drive the degradation of membrane proteins that undergo constitutive internalisation and recycling, including the transferrin receptor and the human cytomegalovirus latency-associated protein US28. We term this approach PACTAC (PCSK9-Antibody Clearance-Targeting Chimeras).
Item Description:Gesehen am 24.10.2024
Physical Description:Online Resource
ISSN:1469-3178
DOI:10.1038/s44319-024-00063-3

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