2Z32

Crystal structure of Keap1 complexed with Prothymosin alpha

Summary for 2Z32

• Entry DOI: 10.2210/pdb2z32/pdb
• Related: 1X2J 1X2R 2DYH
• Descriptor: Kelch-like ECH-associated protein 1, Prothymosin alpha, SULFATE ION, ... (4 entities in total)
• Functional Keywords: kelch domain, b-propellor domain, nrf2 regulation, prothymosin-a interactor, cytoplasm, kelch repeat, nucleus, transcription, transcription regulation, ubl conjugation, acetylation, phosphorylation, structural genomics, nppsfa, national project on protein structural and functional analyses, riken structural genomics/proteomics initiative, rsgi
• Biological source: Mus musculus (house mouse); More
• Cellular location: Cytoplasm: Q9Z2X8; Nucleus: P26350
• Total number of polymer chains: 2
• Total formula weight: 37277.26

Authors

Padmanabhan, B.,Yokoyama, S.,RIKEN Structural Genomics/Proteomics Initiative (RSGI) (deposition date: 2007-05-31, release date: 2008-03-11, Last modification date: 2023-11-01)

Primary citation

Padmanabhan, B.,Nakamura, Y.,Yokoyama, S.
Structural analysis of the complex of Keap1 with a prothymosin alpha peptide
Acta Crystallogr.,Sect.F, 64:233-238, 2008

PubMed 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 (ProTalpha) 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 ProTalpha peptide (amino acids 39-54) has been determined at 1.9 A resolution. The Keap1-bound ProTalpha 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 ProTalpha peptide bind to Keap1 in a similar manner but with different binding potencies.

PubMed: 18391415
DOI: 10.1107/S1744309108004995

Experimental method

X-RAY DIFFRACTION (2 Å)