3fnv

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Revision as of 07:56, 5 December 2018

Crystal Structure of Miner1: The Redox-active 2Fe-2S Protein Causative in Wolfram Syndrome 2

Structural highlights

3fnv is a 2 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	2qh7
Gene:	CDGSH2, CISD2, ERIS, ZCD2 (HUMAN)
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]

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 endoplasmic reticulum protein Miner1 is essential for health and longevity. Mis-splicing of CISD2, which codes for Miner1, is causative in Wolfram Syndrome 2 (WFS2) resulting in early onset optic atrophy, diabetes mellitus, deafness and decreased lifespan. In knock-out studies, disruption of CISD2 leads to accelerated aging, blindness and muscle atrophy. In this work, we characterized the soluble region of human Miner1 and solved its crystal structure to a resolution of 2.1 A (R-factor=17%). Although originally annotated as a zinc finger, we show that Miner1 is a homodimer harboring two redox-active 2Fe-2S clusters, indicating for the first time an association of a redox-active FeS protein with WFS2. Each 2Fe-2S cluster is bound by a rare Cys(3)-His motif within a 17 amino acid segment. Miner1 is the first functionally different protein that shares the NEET fold with its recently identified paralog mitoNEET, an outer mitochondrial membrane protein. We report the first measurement of the redox potentials (E(m)) of Miner1 and mitoNEET, showing that they are proton-coupled with E(m) approximately 0 mV at pH 7.5. Changes in the pH sensitivity of their cluster stabilities are attributed to significant differences in the electrostatic distribution and surfaces between the two proteins. The structural and biophysical results are discussed in relation to possible roles of Miner1 in cellular Fe-S management and redox reactions.

Crystal structure of Miner1: The redox-active 2Fe-2S protein causative in Wolfram Syndrome 2.,Conlan AR, Axelrod HL, Cohen AE, Abresch EC, Zuris J, Yee D, Nechushtai R, Jennings PA, Paddock ML J Mol Biol. 2009 Sep 11;392(1):143-53. Epub 2009 Jul 4. PMID:19580816^[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
↑ Conlan AR, Axelrod HL, Cohen AE, Abresch EC, Zuris J, Yee D, Nechushtai R, Jennings PA, Paddock ML. Crystal structure of Miner1: The redox-active 2Fe-2S protein causative in Wolfram Syndrome 2. J Mol Biol. 2009 Sep 11;392(1):143-53. Epub 2009 Jul 4. PMID:19580816 doi:10.1016/j.jmb.2009.06.079

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

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/3fnv"

@@ Line 1: / Line 1: @@
 ==Crystal Structure of Miner1: The Redox-active 2Fe-2S Protein Causative in Wolfram Syndrome 2==
 <StructureSection load='3fnv' size='340' side='right' caption='[[3fnv]], [[Resolution|resolution]] 2.10&Aring;' scene=''>
@@ Line 6: / Line 7: @@
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2qh7|2qh7]]</td></tr>
 <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">CDGSH2, CISD2, ERIS, ZCD2 ([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=3fnv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fnv OCA], [http://pdbe.org/3fnv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3fnv RCSB], [http://www.ebi.ac.uk/pdbsum/3fnv 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=3fnv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3fnv OCA], [http://pdbe.org/3fnv PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3fnv RCSB], [http://www.ebi.ac.uk/pdbsum/3fnv PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3fnv ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 16: / Line 17: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fn/3fnv_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/fn/3fnv_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>

3fnv

From Proteopedia

Revision as of 07:56, 5 December 2018

Crystal Structure of Miner1: The Redox-active 2Fe-2S Protein Causative in Wolfram Syndrome 2

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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