Cytochrome b explained

Cytochrome b within both molecular and cell biology, is a protein found in the membranes of aerobic cells. In eukaryotic mitochondria (inner membrane) and in aerobic prokaryotes, cytochrome b is a component of respiratory chain complex III — also known as the bc1 complex or ubiquinol-cytochrome c reductase. In plant chloroplasts and cyanobacteria, there is an homologous protein, cytochrome b6, a component of the plastoquinone-plastocyanin reductase, also known as the b6f complex. These complexes are involved in electron transport, the pumping of protons to create a proton-motive force (PMF). This proton gradient is used for the generation of ATP. These complexes play a vital role in cells.^{[1] [2] [3]}

Structure and function

b/b6 is an integral membrane protein of approximately 400 amino acid residues that probably has 8 transmembrane segments. In plants and cyanobacteria, cytochrome b6 consists of two protein subunits encoded by the petB and petD genes. Cytochrome b/b6 non-covalently binds two heme groups, known as b562 and b566. Four conserved histidine residues are postulated to be the ligands of the iron atoms of these two heme groups.^{[2] [3]}

The heme groups are key parts of the internal electron transfer pathway and indespensible to the functioning of the two quinol oxidizing complexes. Two units of b/b6 also form a quinol entry pathway.^[4]

Use in phylogenetics

Cytochrome b is commonly used as a region of mitochondrial DNA for determining phylogenetic relationships between organisms, due to its sequence variability. It is considered to be most useful in determining relationships within families and genera. Comparative studies involving cytochrome b have resulted in new classification schemes and have been used to assign newly described species to a genus as well as to deepen the understanding of evolutionary relationships.^[5]

Clinical significance

Mutations in cytochrome b primarily result in exercise intolerance in human patients; though more rare, severe multi-system pathologies have also been reported.^[6]

Single-point mutations in cytochrome b of Plasmodium falciparum and P. berghei are associated with resistance to the anti-malarial drug atovaquone.^[7]

Human genes

Human genes encoding cytochrome b proteins include:

• CYB5A – cytochrome b5 type A (microsomal)
• CYB5B – cytochrome b5 type B (outer mitochondrial membrane)
• CYBASC3 – cytochrome b, ascorbate dependent 3
• MT-CYB – mitochondrially encoded cytochrome b

Fungicide target

Cyt b is targeted by the QI class of fungicides, Fungicide Resistance Action Committee group 11. The cyt b mutations and provide resistance against the main body of group 11, although G143A does not work against metyltetraprole (11A).^[8] G143A is significant in Botrytis cinerea in California strawberry production.

Notes and References

1. Book: Blankenship, Robert. Molecular Mechanisms of Photosynthesis. 2009. Blackwell Publishing. 124–132.
2. Howell N . Evolutionary conservation of protein regions in the proton motive cytochrome b and their possible roles in redox catalysis . J. Mol. Evol. . 29 . 2 . 157–69 . August 1989 . 2509716 . 10.1007/BF02100114. 1989JMolE..29..157H . 7298013 .
3. Esposti MD, De Vries S, Crimi M, Ghelli A, Patarnello T, Meyer A . Mitochondrial cytochrome b: evolution and structure of the protein . Biochim. Biophys. Acta . 1143 . 3 . 243–71 . July 1993 . 8329437 . 10.1016/0005-2728(93)90197-N.
4. Sarewicz . M . Pintscher . S . Pietras . R . Borek . A . Bujnowicz . Ł . Hanke . G . Cramer . WA . Finazzi . G . Osyczka . A . Catalytic Reactions and Energy Conservation in the Cytochrome bc(1) and b(6)f Complexes of Energy-Transducing Membranes. . Chemical Reviews . 24 February 2021 . 121 . 4 . 2020–2108 . 10.1021/acs.chemrev.0c00712 . 33464892 . 7908018 . free.
5. Castresana . J. . Cytochrome b Phylogeny and the Taxonomy of Great Apes and Mammals . Molecular Biology and Evolution . 18 . 465–471 . 2001 . 11264397 . 4 . 10.1093/oxfordjournals.molbev.a003825. free .
6. Blakely EL, Mitchell AL, Fisher N, Meunier B, Nijtmans LG, Schaefer AM, Jackson MJ, Turnbull DM, Taylor RW . A mitochondrial cytochrome b mutation causing severe respiratory chain enzyme deficiency in humans and yeast . FEBS J. . 272 . 14 . 3583–92 . July 2005 . 16008558 . 10.1111/j.1742-4658.2005.04779.x . 13938075 . free .
7. Siregar JE, Syafruddin D, Matsuoka H, Kita K, Marzuki S . Mutation underlying resistance of Plasmodium berghei to atovaquone in the quinone binding domain 2 (Qo(2)) of the cytochrome b gene . Parasitology International . 57 . 2 . 229–32 . June 2008 . 18248769 . 10.1016/j.parint.2007.12.002 .
8. Web site: FRAC Code List ©*2021: Fungal control agents sorted by cross resistance pattern and mode of action (including coding for FRAC Groups on product labels) . March 2021 . FRAC (Fungicide Resistance Action Committee) . 2021-06-16 . 2021-11-05 . https://web.archive.org/web/20211105005300/https://www.frac.info/docs/default-source/publications/frac-code-list/frac-code-list-2021--final.pdf . dead .