Protein Domain : IPR006248

Type:  Family Name:  Aconitase, mitochondrial-like
Description:  Aconitase (aconitate hydratase; ) is an iron-sulphur protein that contains a [4Fe-4S]-cluster and catalyses the interconversion of isocitrate and citrate via a cis-aconitate intermediate. Aconitase functions in both the TCA and glyoxylate cycles, however unlike the majority of iron-sulphur proteins that function as electron carriers, the [4Fe-4S]-cluster of aconitase reacts directly with an enzyme substrate. In eukaryotes there is a cytosolic form (cAcn) and a mitochondrial form (mAcn) of the enzyme. In bacteria there are also 2 forms, aconitase A (AcnA) and B (AcnB). Several aconitases are known to be multi-functional enzymes with a second non-catalytic, but essential function that arises when the cellular environment changes, such as when iron levels drop [, ]. Eukaryotic cAcn and mAcn, and bacterial AcnA have the same domain organisation, consisting of three N-terminal alpha/beta/alpha domains, a linker region, followed by a C-terminal 'swivel' domain with a beta/beta/alpha structure (1-2-3-linker-4), although mAcn is small than cAcn. However, bacterial AcnB has a different organisation: it contains an N-terminal HEAT-like domain, followed by the 'swivel' domain, then the three alpha/beta/alpha domains (HEAT-4-1-2-3) []. Below is a description of some of the multi-functional activities associated with different aconitases.Eukaryotic mAcn catalyses the second step of the mitochondrial TCA cycle, which is important for energy production, providing high energy electrons in the form of NADH and FADH2 to the mitochondrial oxidative phosphorylation pathway []. The TCA cycle also provides precursors for haem and amino acid production. This enzyme has a second, non-catalytic but essential role in mitochondrial DNA (mtDNA) maintenance: mAcn acts to stabilise mtDNA, forming part of mtDNA protein-DNA complexes known as nucleoids. mAcn is thought to reversibly model nucleoids to directly influence mitochondrial gene expression in response to changes in the cellular environment. Therefore, mAcn can influence the expression of components of the oxidative phosphorylation pathway encoded in mtDNA. Eukaryotic cAcn enzyme balances the amount of citrate and isocitrate in the cytoplasm, which in turn creates a balance between the amount of NADPH generated from isocitrate by isocitrate dehydrogenase with the amount of acetyl-CoA generated from citrate by citrate lyase. Fatty acid synthesis requires both NADPH and acetyl-CoA, as do other metabolic processes, including the need for NADPH to combat oxidative stress. The enzymatic form of cAcn predominates when iron levels are normal, but if they drop sufficiently to cause the disassembly of the [4Fe-4S]-cluster, then cAcn undergoes a conformational change from a compact enzyme to a more open L-shaped protein known as iron regulatory protein 1 (IRP1; or IRE-binding protein 1, IREBP1) [, ]. As IRP1, the catalytic site and the [4Fe-4S]-cluster are lost, and two new RNA-binding sites appear. IRP1 functions in the post-transcriptional regulation of genes involved in iron metabolism - it binds to mRNA iron-responsive elements (IRE), 30-nucleotide stem-loop structures at the 3' or 5' end of specific transcripts. Transcripts containing an IRE include ferritin L and H subunits (iron storage), transferrin (iron plasma chaperone), transferrin receptor (iron uptake into cells), ferroportin (iron exporter), mAcn, succinate dehydrogenase, erythroid aminolevulinic acid synthetase (tetrapyrrole biosynthesis), among others. If the IRE is in the 5'-UTR of the transcript (e.g. in ferritin mRNA), then IRP1-binding prevents its translation by blocking the transcript from binding to the ribosome. If the IRE is in the 3'-UTR of the transcript (e.g. transferrin receptor), then IRP1-binding protects it from endonuclease degradation, thereby prolonging the half-life of the transcript and enabling it to be translated [].IRP2 is another IRE-binding protein that binds to the same transcripts as IRP1. However, since IRP1 is predominantly in the enzymatic cAcn form, it is IRP2 that acts as the major metabolic regulator that maintains iron homeostasis []. Although IRP2 is homologous to IRP1, IRP2 lacks aconitase activity, and is known only to have a single function in the post-transcriptional regulation of iron metabolism genes []. In iron-replete cells, IRP2 activity is regulated primarily by iron-dependent degradation through the ubiquitin-proteasomal system.Bacterial AcnB is also known to be multi-functional. In addition to its role in the TCA cycle, AcnB was shown to be a post-transcriptional regulator of gene expression in Escherichia coliand Salmonella enterica[, ]. In S. enterica, AcnB initiates a regulatory cascade controlling flagella biosynthesis through an interaction with the ftsH transcript, an alternative RNA polymerase sigma factor. This binding lowers the intracellular concentration of FtsH protease, which in turn enhances the amount of RNA polymerase sigma32 factor (normally degraded by FtsH protease), and sigma32 then increases the synthesis of chaperone DnaK, which in turn promotes the synthesis of the flagellar protein FliC. AcnB regulates the synthesis of other proteins as well, such as superoxide dismutase (SodA) and other enzymes involved in oxidative stress.This entry represents mitochondrial aconitase (mAcn), as well as close homologues such as certain bacterial aconitase A (AcnA) enzymes. Short Name:  Aconitase_mito-like
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0 Child Features

5 Contains

DB identifier Type Name
IPR015931 Domain Aconitase/3-isopropylmalate dehydratase large subunit, alpha/beta/alpha, subdomain 1/3
IPR000573 Domain Aconitase A/isopropylmalate dehydratase small subunit, swivel domain
IPR001030 Domain Aconitase/3-isopropylmalate dehydratase large subunit, alpha/beta/alpha domain
IPR015932 Domain Aconitase/3-isopropylmalate dehydratase large subunit, alpha/beta/alpha, subdomain 2
IPR018136 Binding_site Aconitase family, 4Fe-4S cluster binding site

1 Cross References

Identifier
TIGR01340

0 Found In

3 GO Annotations

GO Term Gene Name
GO:0003994 IPR006248
GO:0051539 IPR006248
GO:0006099 IPR006248

3 Ontology Annotations

GO Term Gene Name
GO:0003994 IPR006248
GO:0051539 IPR006248
GO:0006099 IPR006248

1 Parent Features

DB identifier Type Name
IPR015937 Family Aconitase/isopropylmalate dehydratase

9 Proteins

DB identifier UniProt Accession Secondary Identifier Organism Name Length
27212 I0Z7X7 PAC:27393494 Coccomyxa subellipsoidea C-169 795  
70903 C1N5W5 PAC:27342126 Micromonas pusilla CCMP1545 1527  
60441 C1FF99 PAC:27403616 Micromonas sp RCC299 1514  
Cre01.g042750.t1.2 A0A2K3E7I5 PAC:30789585 Chlamydomonas reinhardtii 828  
Dusal.0090s00020.1.p PAC:33189970 Dunaliella salina 809  
Pum0176s0002.2.p A0A1X6P798 PAC:38008463 Porphyra umbilicalis 727  
Pum0176s0002.1.p A0A1X6P7N1 PAC:38008462 Porphyra umbilicalis 801  
Cz13g00140.t1 PAC:38248118 Chromochloris zofingiensis 838  
Vocar.0001s0673.1.p PAC:32884912 Volvox carteri 824  

11 Publications

First Author Title Year Journal Volume Pages PubMed ID
            9020582
            10087914
            15877277
            16850017
            17513696
            15882410
            15009904
            15543948
            15604397
            16407072
            17185597