title: Structural insights into the similar modes of Nrf2 transcription factor recognition by the cytoplasmic repressor Keap1.
abstract: The cytoplasmic repressor Keap1 regulates the function of transcription factor Nrf2 which plays critical roles in oxidative and xenobiotic stresses. The Neh2 domain of Nrf2 interacts with Keap1 at the bottom region of the Kelch/beta-propeller domain which is formed by double-glycine repeat and C-terminal region domains (Keap1-DC). The structure of Keap1-DC complexed with an Nrf2 peptide containing a conserved DLG motif has been determined at 1.9 A resolution. The Keap1-bound DLG peptide possesses a hairpin conformation, and it binds to the Keap1 protein at the bottom region of the beta-propeller domain. The intermolecular interaction occurs through their complementary electrostatic interactions. Comparison of the present structure with the recently reported Keap1-DC complex structure suggests that the DLG and ETGE motifs of Neh2 in Nrf2 bind to Keap1 in a similar manner but with different binding potencies.
authors.affiliation: Genomic Sciences Center, Yokohama Institute, RIKEN, 1-7-22 Suehiro-cho, Tsurumi, Yokohama 230-0045, Japan.
authors.forename: Balasundaram
authors.initials: B
authors.lastname: Padmanabhan
authors.forename: Kit I
authors.initials: KI
authors.lastname: Tong
authors.forename: Akira
authors.initials: A
authors.lastname: Kobayashi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Shigeyuki
authors.initials: S
authors.lastname: Yokoyama
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry*; D003460:Crystallization; D003593:Cytoplasm / Q000737:chemistry*; D003598:Cytoskeletal Proteins / Q000737:chemistry*; D000072019:Kelch-Like ECH-Associated Protein 1; D008958:Models, Molecular; D051267:NF-E2-Related Factor 2 / Q000737:chemistry*; D018384:Oxidative Stress; D011487:Protein Conformation
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; C117301:Keap1 protein, mouse; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse