1U6D

Crystal structure of the Kelch domain of human Keap1

Summary for 1U6D

• Entry DOI: 10.2210/pdb1u6d/pdb
• Descriptor: kelch-like ECH-associated protein 1 (2 entities in total)
• Functional Keywords: beta-propeller, kelch repeat motif, protein binding
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: Q14145
• Total number of polymer chains: 1
• Total formula weight: 33694.53

Authors

Li, X.,Zhang, D.,Hannink, M.,Beamer, L.J. (deposition date: 2004-07-29, release date: 2004-10-12, Last modification date: 2024-02-14)

Primary citation

Li, X.,Zhang, D.,Hannink, M.,Beamer, L.J.
Crystal structure of the kelch domain of human keap1
J.Biol.Chem., 279:54750-54758, 2004

PubMed Abstract: 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. The structure of the Kelch domain from human Keap1 has been determined by x-ray crystallography to a resolution of 1.85 A. The Kelch domain forms a 6-bladed beta-propeller structure, with residues at the C terminus forming the first strand in the first blade. Key structural roles have been identified for the highly conserved glycine, tyrosine, and tryptophan residues that define the kelch repeat sequence motif. In addition, we show that substitution of a single amino acid located within a loop that extends out from the bottom of the beta-propeller structure abolishes binding of Nrf2. The structure of the Kelch domain of Keap1 represents a high quality model for the superfamily of eukaryotic kelch repeat proteins and provides insight into how disease-causing mutations perturb the structural integrity of the Kelch domain.

PubMed: 15475350
DOI: 10.1074/jbc.M410073200

Experimental method

X-RAY DIFFRACTION (1.85 Å)