1x2r

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[[Image:1x2r.gif|left|200px]]
[[Image:1x2r.gif|left|200px]]
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{{Structure
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|PDB= 1x2r |SIZE=350|CAPTION= <scene name='initialview01'>1x2r</scene>, resolution 1.7&Aring;
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The line below this paragraph, containing "STRUCTURE_1x2r", creates the "Structure Box" on the page.
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{{STRUCTURE_1x2r| PDB=1x2r | SCENE= }}
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|RELATEDENTRY=[[1x2j|1X2J]]
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|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1x2r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1x2r OCA], [http://www.ebi.ac.uk/pdbsum/1x2r PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1x2r RCSB]</span>
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'''Structural basis for the defects of human lung cancer somatic mutations in the repression activity of Keap1 on Nrf2'''
'''Structural basis for the defects of human lung cancer somatic mutations in the repression activity of Keap1 on Nrf2'''
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[[Category: Yamamoto, M.]]
[[Category: Yamamoto, M.]]
[[Category: Yokoyama, S.]]
[[Category: Yokoyama, S.]]
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[[Category: beta propeller]]
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[[Category: Beta propeller]]
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[[Category: national project on protein structural and functional analyse]]
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[[Category: National project on protein structural and functional analyse]]
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[[Category: nppsfa]]
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[[Category: Nppsfa]]
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[[Category: riken structural genomics/proteomics initiative]]
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[[Category: Riken structural genomics/proteomics initiative]]
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[[Category: rsgi]]
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[[Category: Rsgi]]
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[[Category: structural genomic]]
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[[Category: Structural genomic]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sat May 3 14:27:24 2008''
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Revision as of 11:27, 3 May 2008

Image:1x2r.gif

Template:STRUCTURE 1x2r

Structural basis for the defects of human lung cancer somatic mutations in the repression activity of Keap1 on Nrf2


Overview

Nrf2 regulates the cellular oxidative stress response, whereas Keap1 represses Nrf2 through its molecular interaction. To elucidate the molecular mechanism of the Keap1 and Nrf2 interaction, we resolved the six-bladed beta propeller crystal structure of the Kelch/DGR and CTR domains of mouse Keap1 and revealed that extensive inter- and intrablade hydrogen bonds maintain the structural integrity and proper association of Keap1 with Nrf2. A peptide containing the ETGE motif of Nrf2 binds the beta propeller of Keap1 at the entrance of the central cavity on the bottom side via electrostatic interactions with conserved arginine residues. We found a somatic mutation and a gene variation in human lung cancer cells that change glycine to cysteine in the DGR domain, introducing local conformational changes that reduce Keap1's affinity for Nrf2. These results provide a structural basis for the loss of Keap1 function and gain of Nrf2 function.

About this Structure

1X2R is a Protein complex structure of sequences from Mus musculus. Full crystallographic information is available from OCA.

Reference

Structural basis for defects of Keap1 activity provoked by its point mutations in lung cancer., Padmanabhan B, Tong KI, Ohta T, Nakamura Y, Scharlock M, Ohtsuji M, Kang MI, Kobayashi A, Yokoyama S, Yamamoto M, Mol Cell. 2006 Mar 3;21(5):689-700. PMID:16507366 Page seeded by OCA on Sat May 3 14:27:24 2008

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