Acta Crystallographica Section F

Structural Biology and Crystallization Communications

Volume 64, Part 4 (April 2008)

protein structure communications

Acta Cryst. (2008). F64, 233-238 [ doi:10.1107/S1744309108004995 ]

Structural analysis of the complex of Keap1 with a prothymosin peptide

B. Padmanabhan, Y. Nakamura and S. Yokoyama

Abstract: The Nrf2 transcription factor, which plays important roles in oxidative and xenobiotic stress, is negatively regulated by the cytoplasmic repressor Keap1. The [beta] -propeller/Kelch domain of Keap1, which is formed by the double-glycine repeat and C-terminal region domains (Keap1-DC), interacts directly with the Neh2 domain of Nrf2. The nuclear oncoprotein prothymosin [alpha] (ProT [alpha] ) also interacts directly with Keap1 and may play a role in the dissociation of the Keap1-Nrf2 complex. The structure of Keap1-DC complexed with a ProT [alpha] peptide (amino acids 39-54) has been determined at 1.9 Å resolution. The Keap1-bound ProT [alpha] peptide possesses a hairpin conformation and binds to the Keap1 protein at the bottom region of the [beta] -propeller domain. Complex formation occurs as a consequence of their complementary electrostatic interactions. A comparison of the present structure with recently reported Keap1-DC complex structures revealed that the DLG and ETGE motifs of the Neh2 domain of Nrf2 and the ProT [alpha] peptide bind to Keap1 in a similar manner but with different binding potencies.

PDB reference: 2z32

Keywords: oxidative stress; Nrf2 transcription factor; prothymosin ; Keap1; -propeller domain.