The DOI matches its Crossref record; 69 of the 69 references it cites were found in a registry or an index.
Structure of the Keap1:Nrf2 interface provides mechanistic insight into Nrf2 signaling
Open accessAbstract
Keap1 is a BTB-Kelch substrate adaptor protein that regulates steady-state levels of Nrf2, a bZIP transcription factor, in response to oxidative stress. We have determined the structure of the Kelch domain of Keap1 bound to a 16-mer peptide from Nrf2 containing a highly conserved DxETGE motif. The Nrf2 peptide contains two short antiparallel beta-strands connected by two overlapping type I beta-turns stabilized by the aspartate and threonine residues. The beta-turn region fits into a binding pocket on the top face of the Kelch domain and the glutamate residues form multiple hydrogen bonds with highly conserved residues in Keap1. Mutagenesis experiments confirmed the role of individual amino acids for binding of Nrf2 to Keap1 and for Keap1-mediated repression of Nrf2-dependent gene expression. Our results provide a detailed picture of how a BTB-Kelch substrate adaptor protein binds to its cognate substrate and will enable the rational design of novel chemopreventive agents.
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“Crystal structures of peptide substrate complexes have been reported for four BTB-Kelch family members, including KEAP1, KLHL2, KLHL3 and KLHL20 (refs 80,81,82 ).”
From Targeted protein degradation: expanding the toolbox (2019) · cites this paper as [80]
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1 retracted
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Oxidants, oxidative stress and the biology of ageing
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Role of nrf2 in oxidative stress and toxicity
Ma, Q. (2013) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-011112-140320 · Cited by 4,903
“Neh2 interacts with Keap1 DC in a ratio of 1:2 through its ETGE and DLG motifs (43, 49, 50).”
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“104) .”
BackgroundThe Molecular Mechanisms Regulating the KEAP1-NRF2 Pathway
Baird, L., & Yamamoto, M. P. (2020) · Molecular and Cellular Biology · doi:10.1128/mcb.00099-20 · Cited by 1,671
“The loops which connect the -strands form a pocket on the bottom surface of the Kelch domain which provides the interface through which the ETGE motif (79Glu-Thr-Gly-Glu82) within the Neh2 domain of NRF2 binds to KEAP1 (95, 96).”
BackgroundUbiquitin ligases: structure, function, and regulation
Zheng, N., & Shabek, N. (2017) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060815-014922 · Cited by 1,499
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Metadata
- Authors
- Lo, S., Li, X., Henzl, M. T., Beamer, L. J., & Hannink, M.
- Affiliations
- University of Missouri (US)
- Corresponding author
- Beamer, Lesa J
- Hannink, Mark
- Venue
- The EMBO Journal
- Published
- 2006-08-03
- Volume
- 25
- Issue
- 15
- Pages
- 3605-3617
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC1538563
- OpenAlex
- W2141982524
- Cited by
- 604
- References
- 68
- Citations by year
- 2026: 66 · 2025: 66 · 2024: 44 · 2023: 48 · 2022: 47 · 2021: 36 · 2020: 35 · 2019: 23 · 2018: 22 · 2017: 21 · 2016: 25 · 2015: 25 · 2014: 22 · 2013: 34 · 2012: 22
- FWCI
- 4.63
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- The EMBO Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (P50CA103130)
- National Center for Complementary and Integrative Health (AT003899, R01AT003899)
- Lawrence Berkeley National Laboratory
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Ubiquitin and proteasome pathways
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- Keap1, Nrf2, Kelch domain, protein-protein interaction, beta-turn, oxidative stress response, chemoprevention, protein structure
- MeSH terms
- Kelch-Like ECH-Associated Protein 1, Amino Acid Sequence, Animals, Binding Sites, Cells, Cultured, Chlorocebus aethiops, Humans, Models, Molecular, Molecular Sequence Data, Phosphorylation, Protein Binding, Protein Conformation, Signal Transduction, Conserved Sequence, Protein Structure, Tertiary, Dimerization, COS Cells, Amino Acid Motifs, Intracellular Signaling Peptides and Proteins, NF-E2-Related Factor 2
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