Database accession: MF7000750
Name: mitoNEET with M1 molecule
PDB ID: 7p0o
Experimental method: X-ray (1.65 Å)
Assembly: Homodimer
Source organism: Homo sapiens
Primary publication of the structure:
Marjault HB, Karmi O, Zuo K, Michaeli D, Eisenberg-Domovich Y, Rossetti G, de Chassey B, Vonderscher J, Cabantchik I, Carloni P, Mittler R, Livnah O, Meldrum E, Nechushtai R
An anti-diabetic drug targets NEET (CISD) proteins through destabilization of their [2Fe-2S] clusters.
(2022) Commun Biol 5: 437
PMID: 35538231
Abstract:
Elevated levels of mitochondrial iron and reactive oxygen species (ROS) accompany the progression of diabetes, negatively impacting insulin production and secretion from pancreatic cells. In search for a tool to reduce mitochondrial iron and ROS levels, we arrived at a molecule that destabilizes the [2Fe-2S] clusters of NEET proteins (M1). Treatment of db/db diabetic mice with M1 improved hyperglycemia, without the weight gain observed with alternative treatments such as rosiglitazone. The molecular interactions of M1 with the NEET proteins mNT and NAF-1 were determined by X-crystallography. The possibility of controlling diabetes by molecules that destabilize the [2Fe-2S] clusters of NEET proteins, thereby reducing iron-mediated oxidative stress, opens a new route for managing metabolic aberration such as in diabetes.
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
identical protein binding identical protein binding
L-cysteine transaminase activity L-cysteine transaminase activity
metal ion binding metal ion binding
protein homodimerization activity protein homodimerization activity
pyridoxal phosphate binding pyridoxal phosphate binding
Biological process:
protein maturation by [2Fe-2S] cluster transfer protein maturation by [2Fe-2S] cluster transfer
regulation of autophagy regulation of autophagy
regulation of cellular respiration regulation of cellular respiration
Cellular component:
mitochondrial outer membrane mitochondrial outer membrane
mitochondrion mitochondrion
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 1
Source organism: Homo sapiens
Length: 108 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMSLTSSSSVRVEWIAAVTIAAGTAAIGYLAYKRFYVKDHRNKAMINLHIQKDNPKIVHAFDMEDLGDKAVYCRCWRSKKFPFCDGAHTKHNEETGDNVGPLIIKKKET
UniProtKB AC: Q9NZ45 (positions: 42-107)
Coverage: 61%
Name: CDGSH iron-sulfur domain-containing protein 1
Source organism: Homo sapiens
Length: 108 residues
Sequence:Sequence according to the corresponding UniProt protein segmentMSLTSSSSVRVEWIAAVTIAAGTAAIGYLAYKRFYVKDHRNKAMINLHIQKDNPKIVHAFDMEDLGDKAVYCRCWRSKKFPFCDGAHTKHNEETGDNVGPLIIKKKET
UniProtKB AC: Q9NZ45 (positions: 41-106)
Coverage: 61%
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)
Download this entry's XML file (.xml)
Download this entry's JSON file (.json)
