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

Autor:	Schmitt J; Department of Medicine, Cambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge, Hills Road, CB2 0SP, Cambridge, UK.; Faculty of Medicine, Charité Berlin, 10117, Berlin, Germany.; Faculty of Medicine, University of Heidelberg, 69210, Heidelberg, Germany., Poole E; Department of Medicine, Cambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge, Hills Road, CB2 0SP, Cambridge, UK.; Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QP, UK., Groves I; Department of Medicine, Cambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge, Hills Road, CB2 0SP, Cambridge, UK.; Infection Biology, Global Center for Pathogen and Human Health Research, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, 44195, USA., Owen DJ; Cambridge Institute for Medical Research, Keith Peters Building, Hills Road, Cambridge, CB2 0XY, UK. djo30@cam.ac.uk., Graham SC; Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QP, UK. scg34@cam.ac.uk., Sinclair J; Department of Medicine, Cambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge, Hills Road, CB2 0SP, Cambridge, UK. js152@cam.ac.uk., Kelly BT; Cambridge Institute for Medical Research, Keith Peters Building, Hills Road, Cambridge, CB2 0XY, UK. btk1000@cam.ac.uk.
Jazyk:	angličtina
Zdroj:	EMBO reports [EMBO Rep] 2024 Mar; Vol. 25 (3), pp. 951-970. Date of Electronic Publication: 2024 Jan 29.
DOI:	10.1038/s44319-024-00063-3
Abstrakt:	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). (© 2024. The Author(s).)
Databáze:	MEDLINE
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