3ade

Crystal Structure of Keap1 in Complex with Sequestosome-1/p62Crystal Structure of Keap1 in Complex with Sequestosome-1/p62

Structural highlights 3ade is a 2 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.8Å Ligands: Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function KEAP1_MOUSE Retains NFE2L2/NRF2 in the cytosol. Functions as substrate adapter protein for the E3 ubiquitin ligase complex formed by CUL3 and RBX1. Targets NFE2L2/NRF2 for ubiquitination and degradation by the proteasome, thus resulting in the suppression of its transcriptional activity and the repression of antioxidant response element-mediated detoxifying enzyme gene expression. May also retain BPTF in the cytosol. Targets PGAM5 for ubiquitination and degradation by the proteasome (By similarity). Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed Impaired selective turnover of p62 by autophagy causes severe liver injury accompanied by the formation of p62-positive inclusions and upregulation of detoxifying enzymes. These phenotypes correspond closely to the pathological conditions seen in human liver diseases, including alcoholic hepatitis and hepatocellular carcinoma. However, the molecular mechanisms and pathophysiological processes in these events are still unknown. Here we report the identification of a novel regulatory mechanism by p62 of the transcription factor Nrf2, whose target genes include antioxidant proteins and detoxification enzymes. p62 interacts with the Nrf2-binding site on Keap1, a component of Cullin-3-type ubiquitin ligase for Nrf2. Thus, an overproduction of p62 or a deficiency in autophagy competes with the interaction between Nrf2 and Keap1, resulting in stabilization of Nrf2 and transcriptional activation of Nrf2 target genes. Our findings indicate that the pathological process associated with p62 accumulation results in hyperactivation of Nrf2 and delineates unexpected roles of selective autophagy in controlling the transcription of cellular defence enzyme genes. The selective autophagy substrate p62 activates the stress responsive transcription factor Nrf2 through inactivation of Keap1.,Komatsu M, Kurokawa H, Waguri S, Taguchi K, Kobayashi A, Ichimura Y, Sou YS, Ueno I, Sakamoto A, Tong KI, Kim M, Nishito Y, Iemura S, Natsume T, Ueno T, Kominami E, Motohashi H, Tanaka K, Yamamoto M Nat Cell Biol. 2010 Mar;12(3):213-23. Epub 2010 Feb 21. PMID:20173742 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Kelch-like protein 3D structures

spinqualitylabelsall models 3ade, resolution 2.80Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image