2DYH

Crystal structure of the Keap1 protein in complexed with the N-terminal region of the Nrf2 transcription factor

Summary for 2DYH

• Entry DOI: 10.2210/pdb2dyh/pdb
• Related: 1X2J 1X2R
• Descriptor: Kelch-like ECH-associated protein 1, Nrf2/Neh2 peptide from Nuclear factor erythroid 2-related factor 2, SULFATE ION, ... (4 entities in total)
• Functional Keywords: bet-propeller, kelch motif, structural genomics, nppsfa, national project on protein structural and functional analyses, riken structural genomics/proteomics initiative, rsgi, transcription
• Biological source: Mus musculus (mouse); More
• Cellular location: Cytoplasm: Q9Z2X8; Cytoplasm, cytosol: Q60795
• Total number of polymer chains: 2
• Total formula weight: 37479.77

Authors

Padmanabhan, B.,Yokoyama, S.,RIKEN Structural Genomics/Proteomics Initiative (RSGI) (deposition date: 2006-09-14, release date: 2007-09-04, Last modification date: 2023-10-25)

Primary citation

Tong, K.I.,Padmanabhan, B.,Kobayashi, A.,Shang, C.,Hirotsu, Y.,Yokoyama, S.,Yamamoto, M.
Different electrostatic potentials define ETGE and DLG motifs as hinge and latch in oxidative stress response
Mol.Cell.Biol., 27:7511-7521, 2007

PubMed Abstract: Nrf2 is the regulator of the oxidative/electrophilic stress response. Its turnover is maintained by Keap1-mediated proteasomal degradation via a two-site substrate recognition mechanism in which two Nrf2-Keap1 binding sites form a hinge and latch. The E3 ligase adaptor Keap1 recognizes Nrf2 through its conserved ETGE and DLG motifs. In this study, we examined how the ETGE and DLG motifs bind to Keap1 in a very similar fashion but with different binding affinities by comparing the crystal complex of a Keap1-DC domain-DLG peptide with that of a Keap1-DC domain-ETGE peptide. We found that these two motifs interact with the same basic surface of either Keap1-DC domain of the Keap1 homodimer. The DLG motif works to correctly position the lysines within the Nrf2 Neh2 domain for efficient ubiquitination. Together with the results from calorimetric and functional studies, we conclude that different electrostatic potentials primarily define the ETGE and DLG motifs as a hinge and latch that senses the oxidative/electrophilic stress.

PubMed: 17785452
DOI: 10.1128/MCB.00753-07

Experimental method

X-RAY DIFFRACTION (1.9 Å)