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Small-molecule displacement of a cryptic degron causes conditional protein degradation

Open access
Bonger, Kimberly M, Chen, Ling-chun, Liu, Corey W, Wandless, Thomas J·2011·Nature Chemical Biology

Abstract

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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Metadata

Authors
Bonger, K. M., Chen, L.-C., Liu, C. W., & Wandless, T. J.
Venue
Nature Chemical Biology
Published
2011-07-03
Volume
7
Issue
8
Pages
531-537
ISSN
  • 1552-4450 (ISSN-L)
  • 1552-4469
OpenAlex
W2078434863
Cited by
206
References
5
FWCI
3.64
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Small-molecule displacement of a cryptic degron causes conditional protein degradation. https://app.cochat.ai/papers/10.1038/nchembio.598
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Bonger, K. M., Chen, L.-C., Liu, C. W., & Wandless, T. J. (2011). Small-molecule displacement of a cryptic degron causes conditional protein degradation. Nature Chemical Biology. https://doi.org/10.1038/nchembio.598

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