2z32

From Proteopedia

(Difference between revisions)

Revision as of 06:32, 25 December 2014

Crystal structure of Keap1 complexed with Prothymosin alpha

Structural highlights

2z32 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.
Ligands:
Related:	1x2j, 1x2r, 2dyh
Gene:	Keap1 (Mus musculus)
Resources:	FirstGlance, OCA, RCSB, PDBsum

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).^[1] ^[2] [PTMA_MOUSE] Prothymosin alpha may mediate immune function by conferring resistance to certain opportunistic infections.

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

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.

Structural analysis of the complex of Keap1 with a prothymosin alpha peptide.,Padmanabhan B, Nakamura Y, Yokoyama S Acta Crystallogr Sect F Struct Biol Cryst Commun. 2008 Apr 1;64(Pt, 4):233-8. Epub 2008 Mar 21. PMID:18391415^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Itoh K, Wakabayashi N, Katoh Y, Ishii T, Igarashi K, Engel JD, Yamamoto M. Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain. Genes Dev. 1999 Jan 1;13(1):76-86. PMID:9887101
↑ McMahon M, Itoh K, Yamamoto M, Hayes JD. Keap1-dependent proteasomal degradation of transcription factor Nrf2 contributes to the negative regulation of antioxidant response element-driven gene expression. J Biol Chem. 2003 Jun 13;278(24):21592-600. Epub 2003 Apr 7. PMID:12682069 doi:10.1074/jbc.M300931200
↑ Padmanabhan B, Nakamura Y, Yokoyama S. Structural analysis of the complex of Keap1 with a prothymosin alpha peptide. Acta Crystallogr Sect F Struct Biol Cryst Commun. 2008 Apr 1;64(Pt, 4):233-8. Epub 2008 Mar 21. PMID:18391415 doi:10.1107/S1744309108004995

1 Structural highlights
2 Function
3 Evolutionary Conservation
4 Publication Abstract from PubMed
5 See Also
6 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2z32"

@@ Line 3: / Line 3: @@
 == Structural highlights ==
 <table><tr><td colspan='2'>[[2z32]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2Z32 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2Z32 FirstGlance]. <br>
-</td></tr><tr><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene><br>
+</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-<tr><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1x2j|1x2j]], [[1x2r|1x2r]], [[2dyh|2dyh]]</td></tr>
+<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1x2j|1x2j]], [[1x2r|1x2r]], [[2dyh|2dyh]]</td></tr>
-<tr><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Keap1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus])</td></tr>
+<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Keap1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus])</td></tr>
-<tr><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2z32 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2z32 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2z32 RCSB], [http://www.ebi.ac.uk/pdbsum/2z32 PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2z32 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2z32 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=2z32 RCSB], [http://www.ebi.ac.uk/pdbsum/2z32 PDBsum]</span></td></tr>
-<table>
+</table>
+== Function ==
+[[http://www.uniprot.org/uniprot/KEAP1_MOUSE 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).<ref>PMID:9887101</ref> <ref>PMID:12682069</ref>  [[http://www.uniprot.org/uniprot/PTMA_MOUSE PTMA_MOUSE]] Prothymosin alpha may mediate immune function by conferring resistance to certain opportunistic infections.
 == Evolutionary Conservation ==
 [[Image:Consurf_key_small.gif|200px|right]]
@@ Line 34: / Line 36: @@
 </StructureSection>
 [[Category: Mus musculus]]
-[[Category: Padmanabhan, B.]]
+[[Category: Padmanabhan, B]]
-[[Category: RSGI, RIKEN Structural Genomics/Proteomics Initiative.]]
+[[Category: Structural genomic]]
-[[Category: Yokoyama, S.]]
+[[Category: Yokoyama, S]]
 [[Category: B-propellor domain]]
 [[Category: Kelch domain]]
@@ Line 46: / Line 48: @@
 [[Category: Phosphorylation]]
 [[Category: Prothymosin-a interactor]]
-[[Category: Riken structural genomics/proteomics initiative]]
 [[Category: Rsgi]]
-[[Category: Structural genomic]]
 [[Category: Transcription]]
 [[Category: Transcription regulation]]

2z32

From Proteopedia

Revision as of 06:32, 25 December 2014

Crystal structure of Keap1 complexed with Prothymosin alpha

Structural highlights

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

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