Kelch-like ECH-associated protein 1 is a protein that in humans is encoded by the Keap1 gene. [5] Keap1 has four discrete protein domains. The N-terminal Broad complex, Tramtrack and Bric-à-Brac (BTB) domain contains the Cys151 residue, which …

2022年6月20日 · KEAP1 functions as (i) a substrate adaptor for a Cullin 3 (CUL3)-based E3 ubiquitin ligase that targets NRF2 for ubiquitination and proteasomal degradation, and (ii) a cysteine-based sensor for a myriad of physiological and pharmacological NRF2 activators.

2004年12月24日 · The structure of the Kelch domain from human Keap1 has been determined by x-ray crystallography to a resolution of 1.85 Å. The Kelch domain forms a 6-bladed β-propeller structure, with residues at the C terminus forming the first strand in the first blade.

Here we review current progress toward the structure determination of Keap1 and its protein complexes with Cul3, Nrf2 substrate, and small-molecule antagonists. Together the available structures establish a rational three-dimensional model to explain the two-site binding of Nrf2 as well as its efficient ubiquitination.

2020年7月1日 · Keap1 (Kelch ECH-associating protein 1) is the substrate-recognition subunit of the Keap1-Cullin3 (Keap1-Cul3) E3 ubiquitin ligase that binds to and ubiquitinates Nrf2 (nuclear factor erythroid-2-related factor), targeting it for degradation via the 26S proteasome [4].

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 …

Keap1 is mainly composed of the following five domains ( Figure 1A ): NTR domain (1–49 amino acid residues), BTB domain (50–179 amino acid residues) that can interact with Cul3, IVR domain (180–314 amino acid residues), six repetitive DGR domains (315–598 amino acid residues), and the final CTR domain (599–624 amino acid residues) (11, 12).

Keap1 is a substrate adaptor of a Cullin 3-based E3 ubiquitin ligase complex that recognizes Nrf2, and also acts as a cellular sensor for xenobiotics and oxidative stresses. Nrf2 is a transcriptional factor regulating the expression of cytoprotective enzyme genes in response to such stresses.

2004年7月29日 · Keap1 is a substrate adaptor protein for an ubiquitin ligase complex that targets the Nrf2 transcription factor for degradation. Keap1 binds Nrf2 through its C-terminal Kelch domain, which contains six copies of the evolutionarily conserved kelch repeat sequence motif.

2017年3月1日 · Here we summarize the early studies leading to the prediction of the existence of Keap1, followed by the discovery of Keap1 as the main negative regulator of Nrf2. We then describe the available structural information on Keap1, its assembly with Cullin3, and its interaction with Nrf2.