P9WIV9 · NUOG_MYCTU
- ProteinNADH-quinone oxidoreductase subunit G
- GenenuoG
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids806 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
NDH-1 shuttles electrons from NADH, via FMN and iron-sulfur (Fe-S) centers, to quinones in the respiratory chain. The immediate electron acceptor for the enzyme in this species is believed to be menaquinone. Couples the redox reaction to proton translocation (for every two electrons transferred, four hydrogen ions are translocated across the cytoplasmic membrane), and thus conserves the redox energy in a proton gradient (By similarity).
Plays a critical role in M.tuberculosis ability to inhibit apoptosis of infected macrophages; thus helps the bacterium in its struggle to resist the host immune response (PubMed:17658950).
In fact, via a NuoG-dependent mechanism, M.tuberculosis can neutralize NOX2-derived reactive oxygen species (ROS) in order to inhibit TNF-alpha-mediated host cell apoptosis (PubMed:20421951).
Also mediates inhibition of neutrophil apoptosis, leading to delayed activation of naive CD4 T cells (PubMed:22264515).
In fact, via a NuoG-dependent mechanism, M.tuberculosis can neutralize NOX2-derived reactive oxygen species (ROS) in order to inhibit TNF-alpha-mediated host cell apoptosis (PubMed:20421951).
Also mediates inhibition of neutrophil apoptosis, leading to delayed activation of naive CD4 T cells (PubMed:22264515).
Catalytic activity
- a quinone + 5 H+(in) + NADH = a quinol + 4 H+(out) + NAD+
CHEBI:132124 + 5 H+ (in)CHEBI:15378+ CHEBI:57945 = CHEBI:24646 + 4 H+ (out)CHEBI:15378+ CHEBI:57540
Cofactor
Protein has several cofactor binding sites:
Note: Binds 1 [2Fe-2S] cluster per subunit.
Note: Binds 3 [4Fe-4S] clusters per subunit.
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 49 | [2Fe-2S] cluster (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 60 | [2Fe-2S] cluster (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 63 | [2Fe-2S] cluster (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 77 | [2Fe-2S] cluster (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 111 | [4Fe-4S] cluster 1 (UniProtKB | ChEBI) | ||||
Sequence: H | ||||||
Binding site | 115 | [4Fe-4S] cluster 1 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 118 | [4Fe-4S] cluster 1 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 124 | [4Fe-4S] cluster 1 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 164 | [4Fe-4S] cluster 2 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 167 | [4Fe-4S] cluster 2 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 170 | [4Fe-4S] cluster 2 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 214 | [4Fe-4S] cluster 2 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 240 | [4Fe-4S] cluster 3 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 243 | [4Fe-4S] cluster 3 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 247 | [4Fe-4S] cluster 3 (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 275 | [4Fe-4S] cluster 3 (UniProtKB | ChEBI) | ||||
Sequence: C |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | peptidoglycan-based cell wall | |
Cellular Component | plasma membrane | |
Cellular Component | plasma membrane respiratory chain complex I | |
Molecular Function | 2 iron, 2 sulfur cluster binding | |
Molecular Function | 4 iron, 4 sulfur cluster binding | |
Molecular Function | metal ion binding | |
Molecular Function | molybdopterin cofactor binding | |
Molecular Function | NADH dehydrogenase (ubiquinone) activity | |
Molecular Function | quinone binding | |
Biological Process | ATP synthesis coupled electron transport | |
Biological Process | cellular respiration | |
Biological Process | symbiont-mediated suppression of host apoptosis |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameNADH-quinone oxidoreductase subunit G
- EC number
- Alternative names
Gene names
Organism names
- Strain
- Taxonomic lineageBacteria > Actinomycetota > Actinomycetes > Mycobacteriales > Mycobacteriaceae > Mycobacterium > Mycobacterium tuberculosis complex
Accessions
- Primary accessionP9WIV9
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Phenotypes & Variants
Disruption phenotype
Deletion of nuoG in M.tuberculosis reduces its ability to inhibit apoptosis of infected human or mouse macrophages and significantly decreases its virulence in mice (PubMed:17658950).
The apoptogenic phenotype of the mutant strain is significantly reduced in human macrophages treated with caspase-3 and -8 inhibitors, TNF-alpha-neutralizing antibodies, and also after infection of murine TNF(-/-) macrophages. Moreover, incubation of macrophages with inhibitors of reactive oxygen species (ROS) reduces not only the apoptosis induced by the nuoG deletion mutant, but also its capacity to increase macrophage TNF-alpha secretion. The phagosomes infected with the mutant show increased ROS levels compared to M.tuberculosis phagosomes in primary murine and human alveolar macrophages. The increase in nuoG deletion mutant induced ROS and apoptosis is abolished in NOX-2 deficient (gp91(-/-)) macrophages (PubMed:20421951).
Compared to wild-type, the nuoG deletion mutant spreads to a larger number of lung phagocytic cells. Consistent with the shorter lifespan of infected neutrophils, infection with the nuoG mutant results in fewer bacteria per infected neutrophil, accelerated bacterial acquisition by dendritic cells, earlier trafficking of these dendritic cells to lymph nodes, and faster CD4 T cell priming. Neutrophil depletion abrogates accelerated CD4 T cell priming by the nuoG mutant, suggesting that inhibiting neutrophil apoptosis delays adaptive immunity in tuberculosis (PubMed:22264515).
The apoptogenic phenotype of the mutant strain is significantly reduced in human macrophages treated with caspase-3 and -8 inhibitors, TNF-alpha-neutralizing antibodies, and also after infection of murine TNF(-/-) macrophages. Moreover, incubation of macrophages with inhibitors of reactive oxygen species (ROS) reduces not only the apoptosis induced by the nuoG deletion mutant, but also its capacity to increase macrophage TNF-alpha secretion. The phagosomes infected with the mutant show increased ROS levels compared to M.tuberculosis phagosomes in primary murine and human alveolar macrophages. The increase in nuoG deletion mutant induced ROS and apoptosis is abolished in NOX-2 deficient (gp91(-/-)) macrophages (PubMed:20421951).
Compared to wild-type, the nuoG deletion mutant spreads to a larger number of lung phagocytic cells. Consistent with the shorter lifespan of infected neutrophils, infection with the nuoG mutant results in fewer bacteria per infected neutrophil, accelerated bacterial acquisition by dendritic cells, earlier trafficking of these dendritic cells to lymph nodes, and faster CD4 T cell priming. Neutrophil depletion abrogates accelerated CD4 T cell priming by the nuoG mutant, suggesting that inhibiting neutrophil apoptosis delays adaptive immunity in tuberculosis (PubMed:22264515).
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Initiator methionine | 1 | Removed | ||||
Sequence: M | ||||||
Modified residue | 2 | N-acetylthreonine | ||||
Sequence: T | ||||||
Chain | PRO_0000118559 | 2-806 | NADH-quinone oxidoreductase subunit G | |||
Sequence: TQAADTDIRVGQPEMVTLTIDGVEISVPKGTLVIRAAELMGIQIPRFCDHPLLEPVGACRQCLVEVEGQRKPLASCTTVATDDMVVRTQLTSEIADKAQHGVMELLLINHPLDCPMCDKGGECPLQNQAMSNGRTDSRFTEAKRTFAKPINISAQVLLDRERCILCARCTRFSDQIAGDPFIDMQERGALQQVGIYADEPFESYFSGNTVQICPVGALTGTAYRFRARPFDLVSSPSVCEHCASGCAQRTDHRRGKVLRRLAGDDPEVNEEWNCDKGRWAFTYATQPDVITTPLIRDGGDPKGALVPTSWSHAMAVAAQGLAAARGRTGVLVGGRVTWEDAYAYAKFARITLGTNDIDFRARPHSAEEADFLAARIAGRHMAVSYADLESAPVVLLVGFEPEDESPIVFLRLRKAARRHRVPVYTIAPFATGGLHKMSGRLIKTVPGGEPAALDDLATGAVGDLLATPGAVIIVGERLATVPGGLSAAARLADTTGARLAWVPRRAGERGALEAGALPTLLPGGRPLADEVARAQVCAAWHIAELPAAAGRDADGILAAAADETLAALLVGGIEPADFADPDAVLAALDATGFVVSLELRHSTVTERADVVFPVAPTTQKAGAFVNWEGRYRTFEPALRGSTLQAGQSDHRVLDALADDMGVHLGVPTVEAAREELAALGIWDGKHAAGPHIAATGPTQPEAGEAILTGWRMLLDEGRLQDGEPYLAGTARTPVVRLSPDTAAEIGAADGEAVTVSTSRGSITLPCSVTDMPDRVVWLPLNSAGSTVHRQLRVTIGSIVKIGAGS |
Keywords
- PTM
Proteomic databases
PTM databases
Interaction
Subunit
The type I NADH dehydrogenase consists of 14 different subunits.
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 15-93 | 2Fe-2S ferredoxin-type | ||||
Sequence: EMVTLTIDGVEISVPKGTLVIRAAELMGIQIPRFCDHPLLEPVGACRQCLVEVEGQRKPLASCTTVATDDMVVRTQLTS | ||||||
Domain | 95-134 | 4Fe-4S His(Cys)3-ligated-type | ||||
Sequence: IADKAQHGVMELLLINHPLDCPMCDKGGECPLQNQAMSNG | ||||||
Domain | 233-289 | 4Fe-4S Mo/W bis-MGD-type | ||||
Sequence: LVSSPSVCEHCASGCAQRTDHRRGKVLRRLAGDDPEVNEEWNCDKGRWAFTYATQPD |
Sequence similarities
Belongs to the complex I 75 kDa subunit family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length806
- Mass (Da)85,424
- Last updated2014-04-16 v1
- Checksum519A1EA833181064
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AL123456 EMBL· GenBank· DDBJ | CCP45962.1 EMBL· GenBank· DDBJ | Genomic DNA |