Figure 1.

(A) The sequence of the Kelch domains from the Keap1 protein of five different species (human, mouse, zebrafish, Drosophila melanogaster, and Anopheles gambia) is shown, along with the sequence of three human BTB-Kelch proteins, mayven, gigaxonin, and ENC1. The six blades of the β-propeller structure are indicated above the alignment and the four β-strands (A–D) that comprise each blade are highlighted in gray. The A strand for blade I is located at the extreme C-terminus of the protein. Disease-associated mutations in Keap1, gigaxonin, and ENC1 proteins are underlined in bold (Bomont et al, 2000, 2003; Bruno et al, 2004; Kuhlenbaumer et al, 2002; Liang et al, 2004; Padmanabhan et al, 2006). Highly conserved residues that define the Kelch repeat are indicated by asterisks. Amino acids in Keap1 whose side chains contact the Nrf2-derived peptide in the crystal structure are highlighted in blue, whereas those amino acids that only make van der Waals contacts with the Nrf2-derived peptide are highlighted in green. (B) The Neh2 domain from the human Nrf1 and Nrf2 proteins is shown, along with the corresponding regions of Nrf2-related proteins from zebrafish and D. melanogaster. Two conserved motifs that have been implicated in binding to Keap1 are shown. The glutamate residues of the DxETGE motif are highlighted in blue. The sequence of the three Nrf2-derived peptides used in our experiments is shown.