4ooa

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Revision as of 12:24, 11 August 2016

CRYSTAL STRUCTURE of NAF1 (MINER1): H114C THE REDOX-ACTIVE 2FE-2S PROTEIN

Structural highlights

4ooa is a 6 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	4oo7
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[CISD2_HUMAN] Defects in CISD2 are the cause of Wolfram syndrome type 2 (WFS2) [MIM:604928]. A rare disorder characterized by juvenile-onset insulin-dependent diabetes mellitus with optic atrophy. Other manifestations include diabetes insipidus, sensorineural deafness, dementia, psychiatric illnesses. WFS2 patients additionally show a strong bleeding tendency and gastrointestinal ulceration. Diabetes insipidus may be absent.^[1]

Function

[CISD2_HUMAN] Regulator of autophagy that contributes to antagonize BECN1-mediated cellular autophagy at the endoplasmic reticulum. Participates in the interaction of BCL2 with BECN1 and is required for BCL2-mediated depression of endoplasmic reticulum Ca(2+) stores during autophagy. Contributes to BIK-initiated autophagy, while it is not involved in BIK-dependent activation of caspases. Involved in life span control, probably via its function as regulator of autophagy.^[2] ^[3]

Publication Abstract from PubMed

NAF-1 is an important [2Fe-2S] NEET protein associated with human health and disease. A mis-splicing mutation in NAF-1 results in Wolfram Syndrome type 2, a lethal childhood disease. Upregulation of NAF-1 is found in epithelial breast cancer cells, and suppression of NAF-1 expression by knockdown significantly suppresses tumor growth. Key to NAF-1 function is the NEET fold with its [2Fe-2S] cluster. In this work, the high-resolution structure of native NAF-1 was determined to 1.65 A resolution (R factor = 13.5%) together with that of a mutant in which the single His ligand of its [2Fe-2S] cluster, His114, was replaced by Cys. The NAF-1 H114C mutant structure was determined to 1.58 A resolution (R factor = 16.0%). All structural differences were localized to the cluster binding site. Compared with native NAF-1, the [2Fe-2S] clusters of the H114C mutant were found to (i) be 25-fold more stable, (ii) have a redox potential that is 300 mV more negative and (iii) have their cluster donation/transfer function abolished. Because no global structural differences were found between the mutant and the native (wild-type) NAF-1 proteins, yet significant functional differences exist between them, the NAF-1 H114C mutant is an excellent tool to decipher the underlying biological importance of the [2Fe-2S] cluster of NAF-1 in vivo.

A point mutation in the [2Fe-2S] cluster binding region of the NAF-1 protein (H114C) dramatically hinders the cluster donor properties.,Tamir S, Eisenberg-Domovich Y, Conlan AR, Stofleth JT, Lipper CH, Paddock ML, Mittler R, Jennings PA, Livnah O, Nechushtai R Acta Crystallogr D Biol Crystallogr. 2014 Jun;70(Pt 6):1572-8. doi:, 10.1107/S1399004714005458. Epub 2014 May 23. PMID:24914968^[4]

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

References

↑ Amr S, Heisey C, Zhang M, Xia XJ, Shows KH, Ajlouni K, Pandya A, Satin LS, El-Shanti H, Shiang R. A homozygous mutation in a novel zinc-finger protein, ERIS, is responsible for Wolfram syndrome 2. Am J Hum Genet. 2007 Oct;81(4):673-83. Epub 2007 Aug 20. PMID:17846994 doi:10.1086/520961
↑ Amr S, Heisey C, Zhang M, Xia XJ, Shows KH, Ajlouni K, Pandya A, Satin LS, El-Shanti H, Shiang R. A homozygous mutation in a novel zinc-finger protein, ERIS, is responsible for Wolfram syndrome 2. Am J Hum Genet. 2007 Oct;81(4):673-83. Epub 2007 Aug 20. PMID:17846994 doi:10.1086/520961
↑ Chang NC, Nguyen M, Germain M, Shore GC. Antagonism of Beclin 1-dependent autophagy by BCL-2 at the endoplasmic reticulum requires NAF-1. EMBO J. 2010 Feb 3;29(3):606-18. doi: 10.1038/emboj.2009.369. Epub 2009 Dec 10. PMID:20010695 doi:10.1038/emboj.2009.369
↑ Tamir S, Eisenberg-Domovich Y, Conlan AR, Stofleth JT, Lipper CH, Paddock ML, Mittler R, Jennings PA, Livnah O, Nechushtai R. A point mutation in the [2Fe-2S] cluster binding region of the NAF-1 protein (H114C) dramatically hinders the cluster donor properties. Acta Crystallogr D Biol Crystallogr. 2014 Jun;70(Pt 6):1572-8. doi:, 10.1107/S1399004714005458. Epub 2014 May 23. PMID:24914968 doi:http://dx.doi.org/10.1107/S1399004714005458

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

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

@@ Line 1: / Line 1: @@
 ==CRYSTAL STRUCTURE of NAF1 (MINER1): H114C THE REDOX-ACTIVE 2FE-2S PROTEIN==
 <StructureSection load='4ooa' size='340' side='right' caption='[[4ooa]], [[Resolution|resolution]] 1.58&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=FES:FE2/S2+(INORGANIC)+CLUSTER'>FES</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4oo7|4oo7]]</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=4ooa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ooa OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ooa RCSB], [http://www.ebi.ac.uk/pdbsum/4ooa 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=4ooa FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ooa OCA], [http://pdbe.org/4ooa PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4ooa RCSB], [http://www.ebi.ac.uk/pdbsum/4ooa PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4ooa ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 19: / Line 20: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4ooa" style="background-color:#fffaf0;"></div>
 == References ==
 <references/>

4ooa

From Proteopedia

Revision as of 12:24, 11 August 2016

CRYSTAL STRUCTURE of NAF1 (MINER1): H114C THE REDOX-ACTIVE 2FE-2S PROTEIN

Structural highlights

Disease

Function

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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