Cargando…
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...
Autores principales: | , , , |
---|---|
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 |
_version_ | 1782208491175280640 |
---|---|
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. |
format | Online Article Text |
id | pubmed-3139708 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2011 |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT bongerkimberlym smallmoleculedisplacementofacrypticdegroncausesconditionalproteindegradation AT chenlingchun smallmoleculedisplacementofacrypticdegroncausesconditionalproteindegradation AT liucoreyw smallmoleculedisplacementofacrypticdegroncausesconditionalproteindegradation AT wandlessthomasj smallmoleculedisplacementofacrypticdegroncausesconditionalproteindegradation |