NDUFA11: Difference between revisions

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==Structure==
==Structure==
The NDUFA11 gene is located on the p arm of [[chromosome 19]] in position 13.3 and spans 12,738 base pairs.<ref name = "entrez"/> The gene produces a 15 kDa protein composed of 141 [[amino acids]].<ref name="url_COPaKB">{{cite web | url = http://www.heartproteome.org/copa/ProteinInfo.aspx?QType=Protein%20ID&QValue=Q86Y39 | work = Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) | title = NDUFA11 - NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 11 }}</ref> NDUFA11 is a subunit of the enzyme [[NADH dehydrogenase (ubiquinone)]], the largest of the respiratory complexes. The structure is L-shaped with a long, [[hydrophobic]] [[transmembrane]] domain and a [[hydrophilic]] domain for the peripheral arm that includes all the known redox centers and the NADH binding site.<ref name = Biochem /> It has been noted that the [[N-terminus|N-terminal]] hydrophobic domain has the potential to be folded into an [[alpha helix]] spanning the inner [[mitochondrion|mitochondrial membrane]] with a [[C-terminus|C-terminal]] hydrophilic domain interacting with globular subunits of Complex I. The highly [[conserved sequence|conserved]] two-domain structure suggests that this feature is critical for the protein function and that the hydrophobic domain acts as an anchor for the [[NADH dehydrogenase (ubiquinone)]] complex at the inner mitochondrial membrane. NDUFA11 is one of about 31 hydrophobic subunits that form the transmembrane region of Complex I, but it is an accessory subunit that is believed not to be involved in catalysis.<ref>{{cite web|title=NDUFA11 |url=http://www.uniprot.org/uniprot/Q86Y39|website=UniProt.org|publisher=The UniProt Consortium}}</ref> The predicted [[secondary structure]] is primarily alpha helix, but the carboxy-terminal half of the protein has high potential to adopt a coiled-coil form. The amino-terminal part contains a putative beta sheet rich in hydrophobic amino acids that may serve as mitochondrial import signal.<ref name="pmid9763677"/><ref name="entrez"/><ref name="pmid9425316">{{cite journal | vauthors = Ton C, Hwang DM, Dempsey AA, Liew CC | title = Identification and primary structure of five human NADH-ubiquinone oxidoreductase subunits | journal = Biochemical and Biophysical Research Communications | volume = 241 | issue = 2 | pages = 589–94 | date = Dec 1997 | pmid = 9425316 | pmc =  | doi = 10.1006/bbrc.1997.7707 }}</ref>
The NDUFA11 gene is located on the p arm of [[chromosome 19]] in position 13.3 and spans 12,738 base pairs.<ref name = "entrez"/> The gene produces a 15 kDa protein composed of 141 [[amino acids]].<ref name=COPaKB>{{cite journal | vauthors = Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS, Deng N, Kim AK, Choi JH, Zelaya I, Liem D, Meyer D, Odeberg J, Fang C, Lu HJ, Xu T, Weiss J, Duan H, Uhlen M, Yates JR, Apweiler R, Ge J, Hermjakob H, Ping P | title = Integration of cardiac proteome biology and medicine by a specialized knowledgebase | journal = Circulation Research | volume = 113 | issue = 9 | pages = 1043–53 | date = Oct 2013 | pmid = 23965338 | pmc = 4076475 | doi = 10.1161/CIRCRESAHA.113.301151 }}</ref><ref name="url_COPaKB">{{cite web | url = https://amino.heartproteome.org/web/protein/Q86Y39 | work = Cardiac Organellar Protein Atlas Knowledgebase (COPaKB) | title = NDUFA11 - NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 11 }}</ref> NDUFA11 is a subunit of the enzyme [[NADH dehydrogenase (ubiquinone)]], the largest of the respiratory complexes. The structure is L-shaped with a long, [[hydrophobic]] [[transmembrane]] domain and a [[hydrophilic]] domain for the peripheral arm that includes all the known redox centers and the NADH binding site.<ref name = Biochem /> It has been noted that the [[N-terminus|N-terminal]] hydrophobic domain has the potential to be folded into an [[alpha helix]] spanning the inner [[mitochondrion|mitochondrial membrane]] with a [[C-terminus|C-terminal]] hydrophilic domain interacting with globular subunits of Complex I. The highly [[conserved sequence|conserved]] two-domain structure suggests that this feature is critical for the protein function and that the hydrophobic domain acts as an anchor for the [[NADH dehydrogenase (ubiquinone)]] complex at the inner mitochondrial membrane. NDUFA11 is one of about 31 hydrophobic subunits that form the transmembrane region of Complex I, but it is an accessory subunit that is believed not to be involved in catalysis.<ref>{{cite web|title=NDUFA11 |url=https://www.uniprot.org/uniprot/Q86Y39|website=UniProt.org|publisher=The UniProt Consortium}}</ref> The predicted [[secondary structure]] is primarily alpha helix, but the carboxy-terminal half of the protein has high potential to adopt a coiled-coil form. The amino-terminal part contains a putative beta sheet rich in hydrophobic amino acids that may serve as mitochondrial import signal.<ref name="pmid9763677"/><ref name="entrez"/><ref name="pmid9425316">{{cite journal | vauthors = Ton C, Hwang DM, Dempsey AA, Liew CC | title = Identification and primary structure of five human NADH-ubiquinone oxidoreductase subunits | journal = Biochemical and Biophysical Research Communications | volume = 241 | issue = 2 | pages = 589–94 | date = Dec 1997 | pmid = 9425316 | pmc =  | doi = 10.1006/bbrc.1997.7707 }}</ref>


== Function ==
== Function ==

Latest revision as of 22:26, 18 July 2018

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Identifiers
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External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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UniProt

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Wikidata
View/Edit Human

NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 11 is an enzyme that in humans is encoded by the NDUFA11 gene.[1] The NDUFA11 protein is a subunit of NADH dehydrogenase (ubiquinone), which is located in the mitochondrial inner membrane and is the largest of the five complexes of the electron transport chain[2][3] Mutations in subunits of NADH dehydrogenase (ubiquinone), also known as Complex I, frequently lead to complex neurodegenerative diseases such as Leigh's syndrome. Mutations in this gene are associated with severe mitochondrial complex I deficiency.[4]

Structure

The NDUFA11 gene is located on the p arm of chromosome 19 in position 13.3 and spans 12,738 base pairs.[4] The gene produces a 15 kDa protein composed of 141 amino acids.[5][6] NDUFA11 is a subunit of the enzyme NADH dehydrogenase (ubiquinone), the largest of the respiratory complexes. The structure is L-shaped with a long, hydrophobic transmembrane domain and a hydrophilic domain for the peripheral arm that includes all the known redox centers and the NADH binding site.[2] It has been noted that the N-terminal hydrophobic domain has the potential to be folded into an alpha helix spanning the inner mitochondrial membrane with a C-terminal hydrophilic domain interacting with globular subunits of Complex I. The highly conserved two-domain structure suggests that this feature is critical for the protein function and that the hydrophobic domain acts as an anchor for the NADH dehydrogenase (ubiquinone) complex at the inner mitochondrial membrane. NDUFA11 is one of about 31 hydrophobic subunits that form the transmembrane region of Complex I, but it is an accessory subunit that is believed not to be involved in catalysis.[7] The predicted secondary structure is primarily alpha helix, but the carboxy-terminal half of the protein has high potential to adopt a coiled-coil form. The amino-terminal part contains a putative beta sheet rich in hydrophobic amino acids that may serve as mitochondrial import signal.[3][4][8]

Function

The human NDUFA11 gene codes for a subunit of Complex I of the respiratory chain, which transfers electrons from NADH to ubiquinone.[4] NADH binds to Complex I and transfers two electrons to the isoalloxazine ring of the flavin mononucleotide (FMN) prosthetic arm to form FMNH2. The electrons are transferred through a series of iron-sulfur (Fe-S) clusters in the prosthetic arm and finally to coenzyme Q10 (CoQ), which is reduced to ubiquinol (CoQH2). The flow of electrons changes the redox state of the protein, resulting in a conformational change and pK shift of the ionizable side chain, which pumps four hydrogen ions out of the mitochondrial matrix.[2]

Clinical significance

Mutations in NDUFA11 and other Complex I subunit genes result in mitochondrial Complex I deficiency with autosomal recessive inheritance. Patients with these mutations display a wide range of clinical disorders and phenotypes, including lethal neonatal disease, adult-onset neurodegenerative disorders, macrocephaly with progressive leukodystrophy, nonspecific encephalopathy, hypertrophic cardiomyopathy, myopathy, liver disease, Leigh's syndrome, Leber's hereditary optic neuropathy, and some forms of Parkinson's disease. There is no clear genotype-phenotype correlation, but most cases result from mutations in nuclear-encoded genes rather than mitochondrially-encoded genes.[9]

References

  1. ↑ Loeffen JL, Triepels RH, van den Heuvel LP, Schuelke M, Buskens CA, Smeets RJ, Trijbels JM, Smeitink JA (Dec 1998). "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. doi:10.1006/bbrc.1998.9786. PMID 9878551.
  2. ↑ 2.0 2.1 2.2 Voet D, Voet JG, Pratt CW (2013). "Chapter 18". Fundamentals of biochemistry: life at the molecular level (4th ed.). Hoboken, NJ: Wiley. pp. 581–620. ISBN 978-0-470-54784-7.
  3. ↑ 3.0 3.1 Emahazion T, Beskow A, Gyllensten U, Brookes AJ (Nov 1998). "Intron based radiation hybrid mapping of 15 complex I genes of the human electron transport chain". Cytogenetics and Cell Genetics. 82 (1–2): 115–9. doi:10.1159/000015082. PMID 9763677.
  4. ↑ 4.0 4.1 4.2 4.3 "Entrez Gene: NDUFA11 NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 11".
  5. ↑ Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS, Deng N, Kim AK, Choi JH, Zelaya I, Liem D, Meyer D, Odeberg J, Fang C, Lu HJ, Xu T, Weiss J, Duan H, Uhlen M, Yates JR, Apweiler R, Ge J, Hermjakob H, Ping P (Oct 2013). "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research. 113 (9): 1043–53. doi:10.1161/CIRCRESAHA.113.301151. PMC 4076475. PMID 23965338.
  6. ↑ "NDUFA11 - NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 11". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB).
  7. ↑ "NDUFA11". UniProt.org. The UniProt Consortium.
  8. ↑ Ton C, Hwang DM, Dempsey AA, Liew CC (Dec 1997). "Identification and primary structure of five human NADH-ubiquinone oxidoreductase subunits". Biochemical and Biophysical Research Communications. 241 (2): 589–94. doi:10.1006/bbrc.1997.7707. PMID 9425316.
  9. ↑ "Mitochondrial complex I deficiency". GTR: Genetic Testing Registry. NCBI PubMed. Retrieved 31 March 2015.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

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