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Small molecule displacement of a cryptic degron causes conditional protein degradation

The ability to rapidly regulate the functions of specific proteins in living cells is a valuable tool for biological research. Here we describe a novel technique by which the degradation of a specific protein is induced by a small molecule. A protein of interest is fused to a Ligand-Induced Degradat...

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Detalles Bibliográficos
Autores principales: Bonger, Kimberly M., Chen, Ling-chun, Liu, Corey W., Wandless, Thomas J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3139708/
https://www.ncbi.nlm.nih.gov/pubmed/21725303
http://dx.doi.org/10.1038/nchembio.598
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author Bonger, Kimberly M.
Chen, Ling-chun
Liu, Corey W.
Wandless, Thomas J.
author_facet Bonger, Kimberly M.
Chen, Ling-chun
Liu, Corey W.
Wandless, Thomas J.
author_sort Bonger, Kimberly M.
collection PubMed
description The ability to rapidly regulate the functions of specific proteins in living cells is a valuable tool for biological research. Here we describe a novel technique by which the degradation of a specific protein is induced by a small molecule. A protein of interest is fused to a Ligand-Induced Degradation (LID) domain resulting in the expression of a stable and functional fusion protein. The LID domain is comprised of the FK506- and rapamycin-binding protein (FKBP) and a 19-amino acid degron fused to the C-terminus of FKBP. In the absence of the small molecule Shield-1, the degron binds to the FKBP protein and the fusion protein is stable. Shield-1 binds tightly to FKBP thereby displacing the degron and inducing rapid and processive degradation of the LID domain and any fused partner protein. Structure-function studies of the 19-residue peptide showed that a four-amino acid sequence within the peptide is responsible for degradation.
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spelling pubmed-31397082012-02-01 Small molecule displacement of a cryptic degron causes conditional protein degradation Bonger, Kimberly M. Chen, Ling-chun Liu, Corey W. Wandless, Thomas J. Nat Chem Biol Article The ability to rapidly regulate the functions of specific proteins in living cells is a valuable tool for biological research. Here we describe a novel technique by which the degradation of a specific protein is induced by a small molecule. A protein of interest is fused to a Ligand-Induced Degradation (LID) domain resulting in the expression of a stable and functional fusion protein. The LID domain is comprised of the FK506- and rapamycin-binding protein (FKBP) and a 19-amino acid degron fused to the C-terminus of FKBP. In the absence of the small molecule Shield-1, the degron binds to the FKBP protein and the fusion protein is stable. Shield-1 binds tightly to FKBP thereby displacing the degron and inducing rapid and processive degradation of the LID domain and any fused partner protein. Structure-function studies of the 19-residue peptide showed that a four-amino acid sequence within the peptide is responsible for degradation. 2011-07-03 /pmc/articles/PMC3139708/ /pubmed/21725303 http://dx.doi.org/10.1038/nchembio.598 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Bonger, Kimberly M.
Chen, Ling-chun
Liu, Corey W.
Wandless, Thomas J.
Small molecule displacement of a cryptic degron causes conditional protein degradation
title Small molecule displacement of a cryptic degron causes conditional protein degradation
title_full Small molecule displacement of a cryptic degron causes conditional protein degradation
title_fullStr Small molecule displacement of a cryptic degron causes conditional protein degradation
title_full_unstemmed Small molecule displacement of a cryptic degron causes conditional protein degradation
title_short Small molecule displacement of a cryptic degron causes conditional protein degradation
title_sort small molecule displacement of a cryptic degron causes conditional protein degradation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3139708/
https://www.ncbi.nlm.nih.gov/pubmed/21725303
http://dx.doi.org/10.1038/nchembio.598
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