Structure
MT-ND5 is located in mitochondrial DNA from base pair 12,337 to 14,148.[5] The MT-ND5 gene produces a 67 kDa protein composed of 603 amino acids.[9][10] MT-ND5 is one of seven mitochondrial genes encoding subunits of the enzyme NADH dehydrogenase (ubiquinone), together with MT-ND1, MT-ND2, MT-ND3, MT-ND4, MT-ND4L, and MT-ND6. Also known as Complex I, this enzyme is 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 centres and the NADH binding site. MT-ND5 and the rest of the mitochondrially encoded subunits are the most hydrophobic of the subunits of Complex I and form the core of the transmembrane region.[6]
Function
The MT-ND5 product is a subunit of the respiratory chain Complex I that is supposed to belong to the minimal assembly of core proteins required to catalyze NADH dehydrogenation and electron transfer to ubiquinone (coenzyme Q10).[11] Initially, 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.[6]
References
- 1 2 3 GRCh38: Ensembl release 89: ENSG00000198786 – Ensembl, May 2017
- 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000064367 – Ensembl, May 2017
- ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- 1 2 3 "Entrez Gene: MT-ND5 NADH dehydrogenase subunit 5".
- 1 2 3 Voet D, Voet JG, Pratt CW (2013). "18". Fundamentals of biochemistry : life at the molecular level (4th ed.). Hoboken, NJ: Wiley. pp. 581–620. ISBN 978-0-470-54784-7.
- 1 2 Adam MP, Bick S, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, et al. (1993). "Melas". GeneReviews. PMID 20301411.
- 1 2 "MT-ND5". Genetics Home Reference. US National Library of Medicine. Retrieved 23 March 2015.
- ↑ Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS, et al. (October 2013). "Integration of cardiac proteome biology and medicine by a specialized knowledgebase". Circulation Research. 113 (9): 1043–1053. doi:10.1161/CIRCRESAHA.113.301151. PMC 4076475. PMID 23965338.
- ↑ "NADH-ubiquinone oxidoreductase chain 5". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB).
- ↑ "MT-ND5 - NADH-ubiquinone oxidoreductase chain 5 - Homo sapiens (Human)". UniProt.org: a hub for protein information. The UniProt Consortium.
- ↑ Alston CL, Morak M, Reid C, Hargreaves IP, Pope SA, Land JM, et al. (February 2010). "A novel mitochondrial MTND5 frameshift mutation causing isolated complex I deficiency, renal failure and myopathy". Neuromuscular Disorders. 20 (2): 131–135. doi:10.1016/j.nmd.2009.10.010. PMID 20018511. S2CID 13122341.
- ↑ Taylor RW, Morris AA, Hutchinson M, Turnbull DM (February 2002). "Leigh disease associated with a novel mitochondrial DNA ND5 mutation". European Journal of Human Genetics. 10 (2): 141–144. doi:10.1038/sj.ejhg.5200773. PMID 11938446.
- ↑ Naini AB, Lu J, Kaufmann P, Bernstein RA, Mancuso M, Bonilla E, et al. (March 2005). "Novel mitochondrial DNA ND5 mutation in a patient with clinical features of MELAS and MERRF". Archives of Neurology. 62 (3): 473–476. doi:10.1001/archneur.62.3.473. PMID 15767514.
