Database accession: MF7000748
Name: NAF1 (MINER1)
PDB ID: 4oo7
Experimental method: X-ray (1.65 Å)
Assembly: Homodimer
Source organism: Homo sapiens
Primary publication of the structure:
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.
(2014) Acta Crystallogr. D Biol. Crystallogr. 70: 1572-8
PMID: 24914968
Abstract:
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 Å 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 Å 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.
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: 69-132)
Coverage: 47%
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: 69-135)
Coverage: 49%
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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