Biology:MT-CYB
![]() Generic protein structure example |
Cytochrome b is a protein that in humans is encoded by the MT-CYB gene.[1] Its gene product is a subunit of the respiratory chain protein ubiquinol–cytochrome c reductase (UQCR, complex III or cytochrome bc1 complex), which consists of the products of one mitochondrially encoded gene, MT-CYB (mitochondrial cytochrome b), and ten nuclear genes—UQCRC1, UQCRC2, CYC1, UQCRFS1 (Rieske protein), UQCRB, "11kDa protein", UQCRH (cyt c1 Hinge protein), Rieske protein presequence, "cyt c1 associated protein", and Rieske-associated protein.
Structure
The MT-CYB gene is located on the p arm of mitochondrial DNA in position 12 and spans 1,140 base pairs.[1] The gene produces a 42.7 kDa protein named cytochrome b composed of 380 amino acids.[2][3] Cytochrome b is an integral membrane protein with hydrophobic properties. The catalytic core of the enzyme is composed of eight transmembrane helices, the iron-sulfur protein, and cytochrome c1.[4] Cytochrome b is a fundamental component of the ubiquinol-cytochrome c reductase complex (complex III or cytochrome b-c1 complex) that is part of the mitochondrial respiratory chain. The b-c1 complex mediates electron transfer from ubiquinol to cytochrome c.[5] The structure of the complex is a symmetric homodimer. It is composed of eleven structural subunits, including one mitochondrial genome encoded cytochrome b and ten other nucleus encoded subunits. These subunits include three respiratory subunits (MT-CYB, CYC1 and UQCRFS1), two core proteins (UQCRC1 and UQCRC2) and six low-molecular weight proteins (UQCRH/QCR6, UQCRB/QCR7, UQCRQ/QCR8, UQCR10/QCR9, UQCR11/QCR10 and a cleavage product of UQCRFS1). The total molecular mass of the complex is about 450 kDa.[6][5]
Function
The mitochondrial cytochrome b is fundamental for the assembly and function of Complex III of the mitochondrial respiratory chain.[7] Complex III is responsible for the catalysis of electron transfer from coenzyme Q to cytochrome c in the mitochondrial respiratory chain by translocating protons concomitantly across the inner membrane of the mitochondria.[8][5] The transfer of electrons then contributes to the generation of a proton gradient across the mitochondrial membrane that is then used for ATP synthesis.[5]
Clinical significance
Mutations in MT-CYB can result in mitochondrial deficiencies and associated disorders. It is majorly associated with a complex III deficiency, a deficiency in an enzyme complex which catalyzes electron transfer from coenzyme Q to cytochrome c in the mitochondrial respiratory chain. A complex III deficiency can result in a highly variable phenotype depending on which tissues are affected.[5] Most frequent clinical manifestations include progressive exercise intolerance and cardiomyopathy. Occasional multisystem disorders accompanied by exercise intolerance may arise as well, in forms of deafness, mental retardation, retinitis pigmentosa, cataract, growth retardation, and epilepsy.[5] Other phenotypes include mitochondrial encephalomyopathy, mitochondrial myopathy, Leber hereditary optic neuropathy, muscle weakness, myoglobinuria, blood acidosis, renal tubulopathy, and more.[5][6] Complex III deficiency is known to be rare among mitochondrial diseases and may follow a maternal or mendelian mode of inheritance due to its duality of genetic origin.[4]
References
- ↑ 1.0 1.1 "Entrez Gene: CYTB cytochrome b". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4519.
- ↑ "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.
- ↑ "cytochrome b". Cardiac Organellar Protein Atlas Knowledgebase (COPaKB). https://amino.heartproteome.org/web/protein/P00156.
- ↑ 4.0 4.1 "A neonatal polyvisceral failure linked to a de novo homoplasmic mutation in the mitochondrially encoded cytochrome b gene". Mitochondrion 9 (5): 346–52. September 2009. doi:10.1016/j.mito.2009.06.002. PMID 19563916.
- ↑ 5.0 5.1 5.2 5.3 5.4 5.5 5.6 "UniProtKB - P00156 (CYB_HUMAN)". The UniProt Consortium. https://www.uniprot.org/uniprot/P00156.
- ↑ 6.0 6.1 "Impact of the mitochondrial genetic background in complex III deficiency". PLOS ONE 5 (9): e12801. September 2010. doi:10.1371/journal.pone.0012801. PMID 20862300. Bibcode: 2010PLoSO...512801G.
- ↑ "Exercise intolerance due to cytochrome b mutation". Muscle & Nerve 42 (1): 136–40. July 2010. doi:10.1002/mus.21649. PMID 20544923.
- ↑ "On the mechanism of electron transfer in complex iii of the electron transfer chain". Proceedings of the National Academy of Sciences of the United States of America 57 (3): 798–805. March 1967. doi:10.1073/pnas.57.3.798. PMID 16591533. Bibcode: 1967PNAS...57..798B.
Further reading
- "Mitochondrial genome variation and the origin of modern humans". Nature 408 (6813): 708–13. Dec 2000. doi:10.1038/35047064. PMID 11130070. Bibcode: 2000Natur.408..708I.
- "Major genomic mitochondrial lineages delineate early human expansions". BMC Genetics 2: 13. 2003. doi:10.1186/1471-2156-2-13. PMID 11553319.
- "Reduced-median-network analysis of complete mitochondrial DNA coding-region sequences for the major African, Asian, and European haplogroups". American Journal of Human Genetics 70 (5): 1152–71. May 2002. doi:10.1086/339933. PMID 11938495.
- "Mitochondrial genome diversity of Native Americans supports a single early entry of founder populations into America". American Journal of Human Genetics 71 (1): 187–92. Jul 2002. doi:10.1086/341358. PMID 12022039.
- "Atypical muscle pathology and a survey of cis-mutations in deaf patients harboring a 1555 A-to-G point mutation in the mitochondrial ribosomal RNA gene". Neuromuscular Disorders 12 (5): 506–12. Jun 2002. doi:10.1016/S0960-8966(01)00329-7. PMID 12031626.
- "Natural selection shaped regional mtDNA variation in humans". Proceedings of the National Academy of Sciences of the United States of America 100 (1): 171–6. Jan 2003. doi:10.1073/pnas.0136972100. PMID 12509511. Bibcode: 2003PNAS..100..171M.
- "Mitochondrial myopathy and complex III deficiency in a patient with a new stop-codon mutation (G339X) in the cytochrome b gene". Journal of the Neurological Sciences 209 (1–2): 61–3. May 2003. doi:10.1016/S0022-510X(02)00462-8. PMID 12686403.
- "Mitochondrial genome variation and evolutionary history of Australian and New Guinean aborigines". Genome Research 13 (7): 1600–6. Jul 2003. doi:10.1101/gr.686603. PMID 12840039.
- "Phylogeny of east Asian mitochondrial DNA lineages inferred from complete sequences". American Journal of Human Genetics 73 (3): 671–6. Sep 2003. doi:10.1086/377718. PMID 12870132.
- "Mitochondrial DNA sequence polymorphisms of five ethnic populations from northern China". Human Genetics 113 (5): 391–405. Oct 2003. doi:10.1007/s00439-003-1004-7. PMID 12938036.
- "Mitochondrial DNA transit between West Asia and North Africa inferred from U6 phylogeography". BMC Genetics 4: 15. Oct 2003. doi:10.1186/1471-2156-4-15. PMID 14563219.
- "The deleterious G15498A mutation in mitochondrial DNA-encoded cytochrome b may remain clinically silent in homoplasmic carriers". European Journal of Human Genetics 12 (3): 220–4. Mar 2004. doi:10.1038/sj.ejhg.5201132. PMID 14735157.
- "Phylogeny of mitochondrial DNA macrohaplogroup N in India, based on complete sequencing: implications for the peopling of South Asia". American Journal of Human Genetics 75 (6): 966–78. Dec 2004. doi:10.1086/425871. PMID 15467980.
- "Mitochondrial DNA diversity in indigenous populations of the southern extent of Siberia, and the origins of Native American haplogroups". Annals of Human Genetics 69 (Pt 1): 67–89. Jan 2005. doi:10.1046/j.1529-8817.2003.00127.x. PMID 15638829.
- "Phylogeny and antiquity of M macrohaplogroup inferred from complete mt DNA sequence of Indian specific lineages". BMC Evolutionary Biology 5: 26. 2006. doi:10.1186/1471-2148-5-26. PMID 15804362.
- "Reconstructing the origin of Andaman Islanders". Science 308 (5724): 996. May 2005. doi:10.1126/science.1109987. PMID 15890876.
- "A mitochondrial cytochrome b mutation causing severe respiratory chain enzyme deficiency in humans and yeast". The FEBS Journal 272 (14): 3583–92. Jul 2005. doi:10.1111/j.1742-4658.2005.04779.x. PMID 16008558.
- "The role of selection in the evolution of human mitochondrial genomes". Genetics 172 (1): 373–87. Jan 2006. doi:10.1534/genetics.105.043901. PMID 16172508.
- "The matrilineal ancestry of Ashkenazi Jewry: portrait of a recent founder event". American Journal of Human Genetics 78 (3): 487–97. Mar 2006. doi:10.1086/500307. PMID 16404693.
- "Mitochondrial genomics identifies major haplogroups in Aboriginal Australians". American Journal of Physical Anthropology 131 (2): 282–94. Oct 2006. doi:10.1002/ajpa.20426. PMID 16596590.
![]() | Original source: https://en.wikipedia.org/wiki/MT-CYB.
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