Biology:NDUFS7

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

NADH dehydrogenase [ubiquinone] iron-sulfur protein 7, mitochondrial, also knowns as NADH-ubiquinone oxidoreductase 20 kDa subunit, Complex I-20kD (CI-20kD), or PSST subunit is an enzyme that in humans is encoded by the NDUFS7 gene.[1][2][3] The NDUFS7 protein is a subunit of NADH dehydrogenase (ubiquinone) also known as Complex I, which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain.[4]

Structure

The NDUFS7 gene is located on the p arm of chromosome 19 in position 13.3.[2] The NDUFS7 gene produces a 25 kDa protein composed of 238 amino acids.[5][6] The PSST subunit is highly conserved across evolutionary distances. Crystal structures and mutational studies indicate that it is one of the ubiquinone binding sites of Complex I, together with the TYKY (NDUFS8) subunit.[7] It has been proposed that PSST, along with TYKY, 49 kDa, ND1 and ND5 subunits interact with iron-sulfur clusters as part of the catalytic core of NADH dehydrogenase (ubiquinone).[8]

Function

The PSST subunit encoded by the NDUSF7 gene is one of over 40 subunits involved in the transfer of electrons from NADH to ubiquinone. Specifically, it is thought that the PSST subunit directly couples electron transfer between the iron-sulfur cluster N2 and ubiquinone, along with ubiquinone-binding ND1.[8] Functional evidence for the importance of PSST has been garnered from mutational studies in the obligate aerobic yeast, Yarrow lipolytic, which elucidated a central role in proton translocation that was reduced in mutant forms of the subunit.[9]

Clinical Significance

Mitochondrial complex I deficiency (MT-C1D) is caused by mutations affecting the NDUFS7 gene. Complex I deficiency is a disorder of the mitochondrial respiratory chain that causes a wide range of clinical manifestations, from lethal neonatal disease to adult-onset neurodegenerative disorders. Phenotypes include macrocephaly with progressive leukodystrophy, non-specific encephalopathy, cardiomyopathy, myopathy, liver disease, Leigh syndrome, Leber's hereditary optic neuropathy, and some forms of Parkinson's disease. Leigh syndrome is an early-onset progressive neurodegenerative disorder characterized by the presence of focal, bilateral lesions in one or more areas of the central nervous system including the brainstem, thalamus, basal ganglia, cerebellum and spinal cord, and is the most common mitochondrial encephalomyopathy. Clinical features depend on which areas of the central nervous system are involved and include subacute onset of psychomotor retardation, hypotonia, ataxia, weakness, vision loss, eye movement abnormalities, seizures, dysphagia, and lactic acidosis.[10][3][11]

Interactions

In addition to co-subunits for complex I, NDUFS7 has protein-protein interactions with ENO2 and ARRB2.[12][13]

References

  1. ↑ "Assignment of the PSST subunit gene of human mitochondrial complex I to chromosome 19p13". Genomics 37 (3): 375–80. November 1996. doi:10.1006/geno.1996.0572. PMID 8938450. 
  2. ↑ 2.0 2.1 "Entrez Gene: NDUFS7 NADH dehydrogenase (ubiquinone) Fe-S protein 7, 20kDa (NADH-coenzyme Q reductase)". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=374291. 
  3. ↑ 3.0 3.1 "NDUFS7 - NADH dehydrogenase [ubiquinone iron-sulfur protein 7, mitochondrial precursor - Homo sapiens (Human) - NDUFS7 gene & protein"] (in en). https://www.uniprot.org/uniprot/O75251. 
  4. ↑ Donald Voet; Judith G. Voet; Charlotte W. Pratt (2013). "18". Fundamentals of biochemistry : life at the molecular level (4th ed.). Hoboken, NJ: Wiley. pp. 581–620. ISBN 9780470547847. 
  5. ↑ "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research 113 (9): 1043–53. Oct 2013. doi:10.1161/CIRCRESAHA.113.301151. PMID 23965338. 
  6. ↑ "NADH dehydrogenase [ubiquinone iron-sulfur protein 7, mitochondrial"]. Cardiac Organellar Protein Atlas Knowledgebase (COPaKB). https://amino.heartproteome.org/web/protein/F5GXJ1. 
  7. ↑ "Tracing the tail of ubiquinone in mitochondrial complex I". Biochimica et Biophysica Acta (BBA) - Bioenergetics 1817 (10): 1776–84. October 2012. doi:10.1016/j.bbabio.2012.03.021. PMID 22484275. 
  8. ↑ 8.0 8.1 Schuler, Franz; Casida, John E. (2001-07-02). "Functional coupling of PSST and ND1 subunits in NADH:ubiquinone oxidoreductase established by photoaffinity labeling" (in en). Biochimica et Biophysica Acta (BBA) - Bioenergetics 1506 (1): 79–87. doi:10.1016/S0005-2728(01)00183-9. ISSN 0005-2728. PMID 11418099. 
  9. ↑ "Function of conserved acidic residues in the PSST homologue of complex I (NADH:ubiquinone oxidoreductase) from Yarrowia lipolytica". The Journal of Biological Chemistry 275 (31): 23577–82. August 2000. doi:10.1074/jbc.M002074200. PMID 10811805. http://publikationen.ub.uni-frankfurt.de/files/75842/1-s2.0-S0021925819660138-main.pdf. 
  10. ↑ "Human mitochondrial complex I in health and disease". American Journal of Human Genetics 64 (6): 1505–10. June 1999. doi:10.1086/302432. PMID 10330338. 
  11. ↑ "Leigh syndrome associated with a mutation in the NDUFS7 (PSST) nuclear encoded subunit of complex I". Annals of Neurology 45 (6): 787–90. June 1999. doi:10.1002/1531-8249(199906)45:6<787::AID-ANA13>3.0.CO;2-6. PMID 10360771. https://pure.uva.nl/ws/files/3316861/6031_74050n.pdf. 
  12. ↑ "Interaction Details". IntAct Molecular Interaction Database. https://www.ebi.ac.uk/intact/interaction/EBI-734433?conversationContext=1&kmr=true. 
  13. ↑ "Interaction Details". IntAct Molecular Interaction Database. https://www.ebi.ac.uk/intact/interaction/EBI-736319?conversationContext=1&kmr=true. 

Further reading

  • "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene 138 (1–2): 171–4. January 1994. doi:10.1016/0378-1119(94)90802-8. PMID 8125298. 
  • "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene 200 (1–2): 149–56. October 1997. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149. 
  • "cDNA of eight nuclear encoded subunits of NADH:ubiquinone oxidoreductase: human complex I cDNA characterization completed". Biochemical and Biophysical Research Communications 253 (2): 415–22. December 1998. doi:10.1006/bbrc.1998.9786. PMID 9878551. 
  • "Human complex I defects can be resolved by monoclonal antibody analysis into distinct subunit assembly patterns". The Journal of Biological Chemistry 276 (12): 8892–7. March 2001. doi:10.1074/jbc.M009903200. PMID 11112787. 
  • "Functional coupling of PSST and ND1 subunits in NADH:ubiquinone oxidoreductase established by photoaffinity labeling". Biochimica et Biophysica Acta (BBA) - Bioenergetics 1506 (1): 79–87. July 2001. doi:10.1016/S0005-2728(01)00183-9. PMID 11418099. 
  • "Differences in assembly or stability of complex I and other mitochondrial OXPHOS complexes in inherited complex I deficiency". Human Molecular Genetics 13 (6): 659–67. March 2004. doi:10.1093/hmg/ddh071. PMID 14749350. 
  • "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): 773–86. June 2004. doi:10.1016/j.cell.2004.05.008. PMID 15186778. 
  • "A novel mutation in the human complex I NDUFS7 subunit associated with Leigh syndrome". Molecular Genetics and Metabolism 90 (4): 379–82. April 2007. doi:10.1016/j.ymgme.2006.12.007. PMID 17275378. 
  • "A novel mutation of the NDUFS7 gene leads to activation of a cryptic exon and impaired assembly of mitochondrial complex I in a patient with Leigh syndrome". Molecular Genetics and Metabolism 92 (1–2): 104–8. 2007. doi:10.1016/j.ymgme.2007.05.010. PMID 17604671. 



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