Biology:NDUFS1
 Generic protein structure example |
NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial (NDUFS1) is an enzyme that in humans is encoded by the NDUFS1 gene.[1] The encoded protein, NDUFS1, is the largest subunit of complex I, located on the inner mitochondrial membrane, and is important for mitochondrial oxidative phosphorylation. Mutations in this gene are associated with complex I deficiency.[2]
Structure
NDUFS1 is located on the q arm of chromosome 2 in position 33.3 and has 20 exons.[3] The NDUFS1 gene produces a 79.5 kDa protein composed of 727 amino acids.[4][5] NDUFS1, the protein encoded by this gene, is a member of the complex I 75 kDa subunit family. It contains a transit peptide, 10 turns, 19 beta strands, 27 alpha helixes, and cofactor binding sites for [2Fe-2S] and [4Fe-4S] clusters. The cluster domains consist of a 79 amino acid 2Fe-2S ferredoxin-type from positions 30–108, a 40 amino acid 4Fe-4S His(Cys)3-ligated-type from positions 108–147, and a 57 amino acid 4Fe-4S Mo/W bis-MGD-type from positions 245–301.[6][7] Several transcript variants encoding different isoforms have been found for this gene.[2]
Function
The protein encoded by this gene belongs to the complex I 75 kDa subunit family. Mammalian complex I is composed of 45 different subunits. It locates at the mitochondrial inner membrane. This protein has NADH dehydrogenase activity and oxidoreductase activity. It transfers electrons from NADH to the respiratory chain. The immediate electron acceptor for the enzyme is believed to be ubiquinone. This protein is the largest subunit of complex I and it is a component of the iron-sulfur (IP) fragment of the enzyme. It may form part of the active site crevice where NADH is oxidized.[2]
Clinical significance
Mutations in the NDUFS1 gene are associated with Mitochondrial Complex I Deficiency, which is autosomal recessive. This deficiency is the most common enzymatic defect of the oxidative phosphorylation disorders.[8][9] Mitochondrial complex I deficiency shows extreme genetic heterogeneity and can be caused by mutation in nuclear-encoded genes or in mitochondrial-encoded genes. There are no obvious genotype–phenotype correlations, and inference of the underlying basis from the clinical or biochemical presentation is difficult, if not impossible.[10] However, the majority of cases are caused by mutations in nuclear-encoded genes.[11][12] It causes a wide range of clinical disorders, ranging from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, nonspecific encephalopathy, hypertrophic cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber hereditary optic neuropathy, and some forms of Parkinson disease.[13]
Interactions
NDUFS1 has been shown to have 124 binary protein-protein interactions including 110 co-complex interactions. NDUFS1 appears to interact with SOAT1, NDUFA9, HLA-B, ECE2, C1QTNF9, GPAA1, STOM, GDI1, ACAP2, EHBP1, MBOAT7, PIGS.[14]
See also
References
- ↑ "Determination of the cDNA sequence for the human mitochondrial 75-kDa Fe-S protein of NADH-coenzyme Q reductase". European Journal of Biochemistry 201 (3): 547–50. November 1991. doi:10.1111/j.1432-1033.1991.tb16313.x. PMID 1935949.
- ↑ 2.0 2.1 2.2 "Entrez Gene: NDUFS1 NADH dehydrogenase (ubiquinone) Fe-S protein 1, 75kDa (NADH-coenzyme Q reductase)". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4719.
This article incorporates text from this source, which is in the public domain.
- ↑ "Entrez Gene: Cytochrome c oxidase assembly factor 7 (putative)". https://www.ncbi.nlm.nih.gov/gene/65260. This article incorporates text from this source, which is in the public domain.
- ↑ Yao, Daniel. "Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) —— Protein Information". https://amino.heartproteome.org/web/protein/P28331.
- ↑ "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research 113 (9): 1043–53. October 2013. doi:10.1161/CIRCRESAHA.113.301151. PMID 23965338.
- ↑ "NDUFS1 - NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial precursor - Homo sapiens (Human) - NDUFS1 gene & protein" (in en). https://www.uniprot.org/uniprot/P28331.
This article incorporates text available under the CC BY 4.0 license.
- ↑ "UniProt: the universal protein knowledgebase". Nucleic Acids Research 45 (D1): D158–D169. January 2017. doi:10.1093/nar/gkw1099. PMID 27899622.
- ↑ "NDUFS6 mutations are a novel cause of lethal neonatal mitochondrial complex I deficiency". The Journal of Clinical Investigation 114 (6): 837–845. September 2004. doi:10.1172/JCI20683. PMID 15372108.
- ↑ "De novo mutations in the mitochondrial ND3 gene as a cause of infantile mitochondrial encephalopathy and complex I deficiency". Annals of Neurology 55 (1): 58–64. January 2004. doi:10.1002/ana.10787. PMID 14705112.
- ↑ "Molecular diagnosis in mitochondrial complex I deficiency using exome sequencing". Journal of Medical Genetics 49 (4): 277–283. April 2012. doi:10.1136/jmedgenet-2012-100846. PMID 22499348. https://epub.ub.uni-muenchen.de/21895/1/oa_21895.pdf.
- ↑ "Isolated complex I deficiency in children: clinical, biochemical and genetic aspects". Human Mutation 15 (2): 123–134. 2000. doi:10.1002/(SICI)1098-1004(200002)15:2<123::AID-HUMU1>3.0.CO;2-P. PMID 10649489.
- ↑ "Respiratory chain complex I deficiency". American Journal of Medical Genetics 106 (1): 37–45. 2001. doi:10.1002/ajmg.1397. PMID 11579423.
- ↑ "Human complex I deficiency: clinical spectrum and involvement of oxygen free radicals in the pathogenicity of the defect". Biochimica et Biophysica Acta (BBA) - Bioenergetics 1364 (2): 271–286. May 1998. doi:10.1016/s0005-2728(98)00033-4. PMID 9593934.
- ↑ "124 binary interactions found for search term NDUFS1". IntAct Molecular Interaction Database. EMBL-EBI. https://www.ebi.ac.uk/intact/interactions?conversationContext=3&query=NDUFS1.
Further reading
- "Teaching NeuroImages: rapidly progressive leukoencephalopathy in mitochondrial complex I deficiency". Neurology 81 (2): e10-1. July 2013. doi:10.1212/WNL.0b013e31829a339b. PMID 23836946.
- "Localization of the human 75-kDal Fe-S protein of NADH-coenzyme Q reductase gene (NDUFS1) to 2q33----q34". Cytogenetics and Cell Genetics 60 (3–4): 212–213. 1992. doi:10.1159/000133340. PMID 1505218.
- "Complex I binds several mitochondrial NAD-coupled dehydrogenases". The Journal of Biological Chemistry 259 (24): 15040–15045. December 1984. doi:10.1016/S0021-9258(17)42511-7. PMID 6439716.
- "cDNA of eight nuclear encoded subunits of NADH:ubiquinone oxidoreductase: human complex I cDNA characterization completed". Biochemical and Biophysical Research Communications 253 (2): 415–422. December 1998. doi:10.1006/bbrc.1998.9786. PMID 9878551.
- "Large-scale deletion and point mutations of the nuclear NDUFV1 and NDUFS1 genes in mitochondrial complex I deficiency". American Journal of Human Genetics 68 (6): 1344–1352. June 2001. doi:10.1086/320603. PMID 11349233.
- "Disruption of mitochondrial function during apoptosis is mediated by caspase cleavage of the p75 subunit of complex I of the electron transport chain". Cell 117 (6): 773–786. June 2004. doi:10.1016/j.cell.2004.05.008. PMID 15186778.
- "Leigh syndrome associated with mitochondrial complex I deficiency due to a novel mutation in the NDUFS1 gene". Archives of Neurology 62 (4): 659–661. April 2005. doi:10.1001/archneur.62.4.659. PMID 15824269.
- "Towards a proteome-scale map of the human protein-protein interaction network". Nature 437 (7062): 1173–1178. October 2005. doi:10.1038/nature04209. PMID 16189514. Bibcode: 2005Natur.437.1173R.
- "Dysfunctions of cellular oxidative metabolism in patients with mutations in the NDUFS1 and NDUFS4 genes of complex I". The Journal of Biological Chemistry 281 (15): 10374–10380. April 2006. doi:10.1074/jbc.M513387200. PMID 16478720.
- "cAMP controls oxygen metabolism in mammalian cells". FEBS Letters 580 (18): 4539–4543. August 2006. doi:10.1016/j.febslet.2006.06.085. PMID 16870178.
External links
- Overview of all the structural information available in the PDB for UniProt: P28331 (NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial) at the PDBe-KB.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
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