Database accession: MF7000741
Name: Miner1
PDB ID: 3fnv
Experimental method: X-ray (2.10 Å)
Assembly: Homodimer
Source organism: Homo sapiens
Primary publication of the structure:
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.
(2009) J. Mol. Biol. 392: 143-53
PMID: 19580816
Abstract:
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.
Annotations from the GeneOntology database. Only terms that fit at least two of the interacting proteins are shown. Molecular function:
2 iron, 2 sulfur cluster binding 2 iron, 2 sulfur cluster binding
metal ion binding metal ion binding
protein homodimerization activity protein homodimerization activity
RNA binding RNA binding
Biological process:
autophagy autophagy
regulation of autophagy regulation of autophagy
Cellular component:
endoplasmic reticulum endoplasmic reticulum
endoplasmic reticulum membrane endoplasmic reticulum membrane
membrane membrane
mitochondrial outer membrane mitochondrial outer membrane
perinuclear endoplasmic reticulum perinuclear endoplasmic reticulum
protein-containing complex protein-containing complex
Structural annotations of the participating protein chains.Entry contents: 2 distinct polypeptide molecules
Chains: A, B
Notes: All chains according to the most probable oligomerization state stored in PDBe were considered.
Number of unique protein segments: 1
Name: CDGSH iron-sulfur domain-containing protein 2
Source organism: Homo sapiens
Length: 135 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMVLESVARIVKVQLPAYLKRLPVPESITGFARLTVSEWLRLLPFLGVLALLGYLAVRPFLPKKKQQKDSLINLKIQKENPKVVNEINIEDLCLTKAAYCRCWRSKTFPACDGSHNKHNELTGDNVGPLILKKKEV
UniProtKB AC: Q8N5K1 (positions: 68-134)
Coverage: 49%
Name: CDGSH iron-sulfur domain-containing protein 2
Source organism: Homo sapiens
Length: 135 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMVLESVARIVKVQLPAYLKRLPVPESITGFARLTVSEWLRLLPFLGVLALLGYLAVRPFLPKKKQQKDSLINLKIQKENPKVVNEINIEDLCLTKAAYCRCWRSKTFPACDGSHNKHNELTGDNVGPLILKKKEV
UniProtKB AC: Q8N5K1 (positions: 68-135)
Coverage: 50%
Evidence demonstrating that the participating proteins are unstructured prior to the interaction and their folding is coupled to binding. Representative domain in related structures: Iron-binding zinc finger CDGSH type
Evidence level: Indirect evidence
Evidence coverage: The full structure participates in mutual synergistic folding.
Complex Evidence:
Size exclusion chromatography measurements suggest that mitoNEET33–108 protein exists as a dimer in solution (PMID:17905743). The monomers associate along their full length to form an intertwined structure with an extensive interface (PMID:17766439).
Chain A:
N/A
Chain B:
N/A
Surface and contacts features:
Structures from the PDB that contain the same number of proteins, and the proteins from the two structures show a sufficient degree of pairwise similarity, i.e. they belong to the same UniRef90 cluster (the full proteins exhibit at least 90% sequence identity) and convey roughly the same region to their respective interactions (the two regions from the two proteins share a minimum of 70% overlap). Download the CIF file (.cif)
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