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4gfx

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Revision as of 07:06, 5 August 2016

Crystal structure of the N-terminal domain of TXNIP

Structural highlights

4gfx is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Gene:	TXNIP, VDUP1 (HUMAN)
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

[TXNIP_HUMAN] May act as an oxidative stress mediator by inhibiting thioredoxin activity or by limiting its bioavailability. Interacts with COPS5 and restores COPS5-induced suppression of CDKN1B stability, blocking the COPS5-mediated translocation of CDKN1B from the nucleus to the cytoplasm. Functions as a transcriptional repressor, possibly by acting as a bridge molecule between transcription factors and corepressor complexes, and over-expression will induce G0/G1 cell cycle arrest. Required for the maturation of natural killer cells. Acts as a suppressor of tumor cell growth. Inhibits the proteasomal degradation of DDIT4, and thereby contributes to the inhibition of the mammalian target of rapamycin complex 1 (mTORC1).^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

The redox-dependent inhibition of thioredoxin (TRX) by thioredoxin-interacting protein (TXNIP) plays a pivotal role in various cancers and metabolic syndromes. However, the molecular mechanism of this regulation is largely unknown. Here, we present the crystal structure of the TRX-TXNIP complex and demonstrate that the inhibition of TRX by TXNIP is mediated by an intermolecular disulphide interaction resulting from a novel disulphide bond-switching mechanism. Upon binding to TRX, TXNIP undergoes a structural rearrangement that involves switching of a head-to-tail interprotomer Cys63-Cys247 disulphide between TXNIP molecules to an interdomain Cys63-Cys190 disulphide, and the formation of a de novo intermolecular TXNIP Cys247-TRX Cys32 disulphide. This disulphide-switching event unexpectedly results in a domain arrangement of TXNIP that is entirely different from those of other arrestin family proteins. We further show that the intermolecular disulphide bond between TRX and TXNIP dissociates in the presence of high concentrations of reactive oxygen species. This study provides insight into TRX and TXNIP-dependent cellular regulation.

The structural basis for the negative regulation of thioredoxin by thioredoxin-interacting protein.,Hwang J, Suh HW, Jeon YH, Hwang E, Nguyen LT, Yeom J, Lee SG, Lee C, Kim KJ, Kang BS, Jeong JO, Oh TK, Choi I, Lee JO, Kim MH Nat Commun. 2014 Jan 6;5:2958. doi: 10.1038/ncomms3958. PMID:24389582^[5]

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

References

↑ Liyanage NP, Fernando MR, Lou MF. Regulation of the bioavailability of thioredoxin in the lens by a specific thioredoxin-binding protein (TBP-2). Exp Eye Res. 2007 Aug;85(2):270-9. Epub 2007 May 21. PMID:17603038 doi:S0014-4835(07)00133-9
↑ Han SH, Jeon JH, Ju HR, Jung U, Kim KY, Yoo HS, Lee YH, Song KS, Hwang HM, Na YS, Yang Y, Lee KN, Choi I. VDUP1 upregulated by TGF-beta1 and 1,25-dihydorxyvitamin D3 inhibits tumor cell growth by blocking cell-cycle progression. Oncogene. 2003 Jun 26;22(26):4035-46. PMID:12821938 doi:10.1038/sj.onc.1206610
↑ Shin KH, Kim RH, Kim RH, Kang MK, Park NH. hnRNP G elicits tumor-suppressive activity in part by upregulating the expression of Txnip. Biochem Biophys Res Commun. 2008 Aug 8;372(4):880-5. doi:, 10.1016/j.bbrc.2008.05.175. Epub 2008 Jun 9. PMID:18541147 doi:10.1016/j.bbrc.2008.05.175
↑ Jin HO, Seo SK, Kim YS, Woo SH, Lee KH, Yi JY, Lee SJ, Choe TB, Lee JH, An S, Hong SI, Park IC. TXNIP potentiates Redd1-induced mTOR suppression through stabilization of Redd1. Oncogene. 2011 Sep 1;30(35):3792-801. doi: 10.1038/onc.2011.102. Epub 2011 Apr 4. PMID:21460850 doi:10.1038/onc.2011.102
↑ Hwang J, Suh HW, Jeon YH, Hwang E, Nguyen LT, Yeom J, Lee SG, Lee C, Kim KJ, Kang BS, Jeong JO, Oh TK, Choi I, Lee JO, Kim MH. The structural basis for the negative regulation of thioredoxin by thioredoxin-interacting protein. Nat Commun. 2014 Jan 6;5:2958. doi: 10.1038/ncomms3958. PMID:24389582 doi:http://dx.doi.org/10.1038/ncomms3958

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4gfx"

Categories: Human | Hwang, J | Kim, M H | Arrestin-like fold | Protein binding

@@ Line 1: / Line 1: @@
 ==Crystal structure of the N-terminal domain of TXNIP==
 <StructureSection load='4gfx' size='340' side='right' caption='[[4gfx]], [[Resolution|resolution]] 1.60&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=GOL:GLYCEROL'>GOL</scene></td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TXNIP, VDUP1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=4gfx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gfx OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4gfx RCSB], [http://www.ebi.ac.uk/pdbsum/4gfx 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=4gfx FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4gfx OCA], [http://pdbe.org/4gfx PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4gfx RCSB], [http://www.ebi.ac.uk/pdbsum/4gfx PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4gfx ProSAT]</span></td></tr>
 </table>
 == Function ==
@@ Line 17: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4gfx" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

4gfx

From Proteopedia

Revision as of 07:06, 5 August 2016

Crystal structure of the N-terminal domain of TXNIP

Structural highlights

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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