Summary: Ubiquinol-cytochrome C reductase complex 14kD subunit
Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.
This is the Wikipedia entry entitled "Coenzyme Q – cytochrome c reductase". More...
Coenzyme Q – cytochrome c reductase Edit Wikipedia article
UCR_TM | |||||||||
---|---|---|---|---|---|---|---|---|---|
Crystal structure of mitochondrial cytochrome bc complex bound with ubiquinone.[1] | |||||||||
Identifiers | |||||||||
Symbol | UCR_TM | ||||||||
Pfam | PF02921 | ||||||||
InterPro | IPR004192 | ||||||||
SCOPe | 1be3 / SUPFAM | ||||||||
TCDB | 3.D.3 | ||||||||
OPM superfamily | 92 | ||||||||
OPM protein | 3cx5 | ||||||||
Membranome | 258 | ||||||||
|
ubiquinol—cytochrome-c reductase | |||||||||
---|---|---|---|---|---|---|---|---|---|
Identifiers | |||||||||
EC number | 7.1.1.8 | ||||||||
CAS number | 9027-03-6 | ||||||||
Databases | |||||||||
IntEnz | IntEnz view | ||||||||
BRENDA | BRENDA entry | ||||||||
ExPASy | NiceZyme view | ||||||||
KEGG | KEGG entry | ||||||||
MetaCyc | metabolic pathway | ||||||||
PRIAM | profile | ||||||||
PDB structures | RCSB PDB PDBe PDBsum | ||||||||
Gene Ontology | AmiGO / QuickGO | ||||||||
|
The coenzyme Q : cytochrome c – oxidoreductase, sometimes called the cytochrome bc1 complex, and at other times complex III, is the third complex in the electron transport chain (EC 1.10.2.2), playing a critical role in biochemical generation of ATP (oxidative phosphorylation). Complex III is a multisubunit transmembrane protein encoded by both the mitochondrial (cytochrome b) and the nuclear genomes (all other subunits). Complex III is present in the mitochondria of all animals and all aerobic eukaryotes and the inner membranes of most eubacteria. Mutations in Complex III cause exercise intolerance as well as multisystem disorders. The bc1 complex contains 11 subunits, 3 respiratory subunits (cytochrome B, cytochrome C1, Rieske protein), 2 core proteins and 6 low-molecular weight proteins.
Ubiquinol—cytochrome-c reductase catalyzes the chemical reaction
- QH2 + 2 ferricytochrome c Q + 2 ferrocytochrome c + 2 H+
Thus, the two substrates of this enzyme are quinol (QH2) and ferri- (Fe3+) cytochrome c, whereas its 3 products are quinone (Q), ferro- (Fe2+) cytochrome c, and H+.
This enzyme belongs to the family of oxidoreductases, specifically those acting on diphenols and related substances as donor with a cytochrome as acceptor. This enzyme participates in oxidative phosphorylation. It has four cofactors: cytochrome c1, cytochrome b-562, cytochrome b-566, and a 2-Iron ferredoxin of the Rieske type.
Contents
Nomenclature
The systematic name of this enzyme class is ubiquinol:ferricytochrome-c oxidoreductase. Other names in common use include:
|
|
Structure
Compared to the other major proton-pumping subunits of the electron transport chain, the number of subunits found can be small, as small as three polypeptide chains. This number does increase, and eleven subunits are found in higher animals.[2] Three subunits have prosthetic groups. The cytochrome b subunit has two b-type hemes (bL and bH), the cytochrome c subunit has one c-type heme (c1), and the Rieske Iron Sulfur Protein subunit (ISP) has a two iron, two sulfur iron-sulfur cluster (2Fe•2S).
Structures of complex III: PDB: 1KYO, PDB: 1L0L
Composition of complex
In vertebrates the bc1 complex, or Complex III, contains 11 subunits: 3 respiratory subunits, 2 core proteins and 6 low-molecular weight proteins.[3][4] Proteobacterial complexes may contain as few as three subunits.[5]
Table of subunit composition of complex III
No. | Subunit name | Human protein | Protein description from UniProt | Pfam family with Human protein |
---|---|---|---|---|
Respiratory subunit proteins | ||||
1 | MT-CYB / Cyt b | CYB_HUMAN | Cytochrome b | Pfam PF13631 |
2 | CYC1 / Cyt c1 | CY1_HUMAN | Cytochrome c1, heme protein, mitochondrial | Pfam PF02167 |
3 | Rieske / UCR1 | UCRI_HUMAN | Cytochrome b-c1 complex subunit Rieske, mitochondrial EC 1.10.2.2 | Pfam PF02921 , Pfam PF00355 |
Core protein subunits | ||||
4 | QCR1 / SU1 | QCR1_HUMAN | Cytochrome b-c1 complex subunit 1, mitochondrial | Pfam PF00675, Pfam PF05193 |
5 | QCR2 / SU2 | QCR2_HUMAN | Cytochrome b-c1 complex subunit 2, mitochondrial | Pfam PF00675, Pfam PF05193 |
Low-molecular weight protein subunits | ||||
6 | QCR6 / SU6 | QCR6_HUMAN | Cytochrome b-c1 complex subunit 6, mitochondrial | Pfam PF02320 |
7 | QCR7 / SU7 | QCR7_HUMAN | Cytochrome b-c1 complex subunit 7 | Pfam PF02271 |
8 | QCR8 / SU8 | QCR8_HUMAN | Cytochrome b-c1 complex subunit 8 | Pfam PF02939 |
9 | QCR9 / SU9 / UCRC | QCR9_HUMANa | Cytochrome b-c1 complex subunit 9 | Pfam PF09165 |
10 | QCR10 / SU10 | QCR10_HUMAN | Cytochrome b-c1 complex subunit 10 | Pfam PF05365 |
11 | QCR11 / SU11 | QCR11_HUMAN | Cytochrome b-c1 complex subunit 11 | Pfam PF08997 |
- a In vertebrates, a cleavage product of 8 kDa from the N-terminus of the Rieske protein (Signal peptide) is retained in the complex as subunit 9. Thus subunits 10 and 11 correspond to fungal QCR9p and QCR10p.
Reaction
It catalyzes the reduction of cytochrome c by oxidation of coenzyme Q (CoQ) and the concomitant pumping of 4 protons from the mitochondrial matrix to the intermembrane space:
- QH2 + 2 cytochrome c (FeIII) + 2 H+
in → Q + 2 cytochrome c (FeII) + 4 H+
out
In the process called Q cycle,[6][7] two protons are consumed from the matrix (M), four protons are released into the inter membrane space (IM) and two electrons are passed to cytochrome c.
Reaction mechanism
The reaction mechanism for complex III (cytochrome bc1, coenzyme Q: cytochrome C oxidoreductase) is known as the ubiquinone ("Q") cycle. In this cycle four protons get released into the positive "P" side (inter membrane space), but only two protons get taken up from the negative "N" side (matrix). As a result, a proton gradient is formed across the membrane. In the overall reaction, two ubiquinols are oxidized to ubiquinones and one ubiquinone is reduced to ubiquinol. In the complete mechanism, two electrons are transferred from ubiquinol to ubiquinone, via two cytochrome c intermediates.
Overall:
- 2 x QH2 oxidised to Q
- 1 x Q reduced to QH2
- 2 x Cyt c reduced
- 4 x H+ released into intermembrane space
- 2 x H+ picked up from matrix
The reaction proceeds according to the following steps:
Round 1:
- Cytochrome b binds a ubiquinol and a ubiquinone.
- The 2Fe/2S center and BL heme each pull an electron off the bound ubiquinol, releasing two hydrogens into the intermembrane space.
- One electron is transferred to cytochrome c1 from the 2Fe/2S centre, whilst another is transferred from the BL heme to the BH Heme.
- Cytochrome c1 transfers its electron to cytochrome c (not to be confused with cytochrome c1), and the BH Heme transfers its electron to a nearby ubiquinone, resulting in the formation of a ubisemiquinone.
- Cytochrome c diffuses. The first ubiquinol (now oxidised to ubiquinone) is released, whilst the semiquinone remains bound.
Round 2:
- A second ubiquinol is bound by cytochrome b.
- The 2Fe/2S center and BL heme each pull an electron off the bound ubiquinol, releasing two hydrogens into the intermembrane space.
- One electron is transferred to cytochrome c1 from the 2Fe/2S centre, whilst another is transferred from the BL heme to the BH Heme.
- Cytocrome c1 then transfers its electron to cytochrome c, whilst the nearby semiquinone produced from round 1 picks up a second electron from the BH heme, along with two protons from the matrix.
- The second ubiquinol (now oxidised to ubiquinone), along with the newly formed ubiquinol are released.[8]
Inhibitors of complex III
There are three distinct groups of Complex III inhibitors.
- Antimycin A binds to the Qi site and inhibits the transfer of electrons in Complex III from heme bH to oxidized Q (Qi site inhibitor).
- Myxothiazol and stigmatellin binds to the Qo site and inhibits the transfer of electrons from reduced QH2 to the Rieske Iron sulfur protein. Myxothiazol and stigmatellin bind to distinct but overlapping pockets within the Qo site.
- Myxothiazol binds nearer to cytochrome bL (hence termed a "proximal" inhibitor).
- Stigmatellin binds farther from heme bL and nearer the Rieske Iron sulfur protein, with which it strongly interacts.
Some have been commercialized as fungicides (the strobilurin derivatives, best known of which is azoxystrobin; QoI inhibitors) and as anti-malaria agents (atovaquone).
Also propylhexedrine inhibits cytochrome c reductase.[9]
Oxygen free radicals
A small fraction of electrons leave the electron transport chain before reaching complex IV. Premature electron leakage to oxygen results in the formation of superoxide. The relevance of this otherwise minor side reaction is that superoxide and other reactive oxygen species are highly toxic and are thought to play a role in several pathologies, as well as aging (the free radical theory of aging).[10] Electron leakage occurs mainly at the Qo site and is stimulated by antimycin A. Antimycin A locks the b hemes in the reduced state by preventing their re-oxidation at the Qi site, which, in turn, causes the steady-state concentrations of the Qo semiquinone to rise, the latter species reacting with oxygen to form superoxide. The effect of high membrane potential is thought to have a similar effect.[11] Superoxide produced at the Qo site can be released both into the mitochondrial matrix[12][13] and into the intermembrane space, where it can then reach the cytosol.[12][14] This could be explained by the fact that Complex III might produce superoxide as membrane permeable HOO• rather than as membrane impermeable O−.
2.[13]
Human gene names
MT-CYB: mtDNA encoded cytochrome b; mutations associated with exercise intolerance
CYC1:cytochrome c1
CYCS: cytochrome c
UQCRFS1: Rieske iron sulfur protein
UQCRB: Ubiquinone binding protein, mutation linked with mitochondrial complex III deficiency nuclear type 3
UQCRH: hinge protein
UQCRC2: Core 2, mutations linked to mitochondrial complex III deficiency, nuclear type 5
UQCRC1: Core 1
UQCR: 6.4KD subunit
UQCR10: 7.2KD subunit
TTC19: Newly identified subunit, mutations linked to complex III deficiency nuclear type 2.
Mutations in complex III genes in human disease
Mutations in complex III-related genes typically manifest as exercise intolerance.[15][16] Other mutations have been reported to cause septo-optic dysplasia[17] and multisystem disorders.[18] However, mutations in BCS1L, a gene responsible for proper maturation of complex III, can result in Björnstad syndrome and the GRACILE syndrome, which in neonates are lethal conditions that have multisystem and neurologic manifestations typifying severe mitochondrial disorders. The pathogenicity of several mutations has been verified in model systems such as yeast.[19]
The extent to which these various pathologies are due to bioenergetic deficits or overproduction of superoxide is presently unknown.
See also
Additional images
References
- ^ PDB: 1ntz; Gao X, Wen X, Esser L, Quinn B, Yu L, Yu CA, Xia D (August 2003). "Structural basis for the quinone reduction in the bc1 complex: a comparative analysis of crystal structures of mitochondrial cytochrome bc1 with bound substrate and inhibitors at the Qi site". Biochemistry. 42 (30): 9067–80. doi:10.1021/bi0341814. PMID 12885240.
- ^ Iwata S, Lee JW, Okada K, Lee JK, Iwata M, Rasmussen B, Link TA, Ramaswamy S, Jap BK (July 1998). "Complete structure of the 11-subunit bovine mitochondrial cytochrome bc1 complex". Science. 281 (5373): 64–71. doi:10.1126/science.281.5373.64. PMID 9651245.
- ^ Zhang Z, Huang L, Shulmeister VM, Chi YI, Kim KK, Hung LW, et al. (1998). "Electron transfer by domain movement in cytochrome bc1". Nature. 392 (6677): 677–84. doi:10.1038/33612. PMID 9565029.
- ^ Hao GF, Wang F, Li H, Zhu XL, Yang WC, Huang LS, et al. (2012). "Computational discovery of picomolar Q(o) site inhibitors of cytochrome bc1 complex". J Am Chem Soc. 134 (27): 11168–76. doi:10.1021/ja3001908. PMID 22690928.
- ^ Yang XH, Trumpower BL (1986). "Purification of a three-subunit ubiquinol-cytochrome c oxidoreductase complex from Paracoccus denitrificans". J Biol Chem. 261 (26): 12282–9. PMID 3017970.
- ^ Kramer DM, Roberts AG, Muller F, Cape J, Bowman MK (2004). Q-cycle bypass reactions at the Qo site of the cytochrome bc1 (and related) complexes. Meth. Enzymol. Methods in Enzymology. 382. pp. 21–45. doi:10.1016/S0076-6879(04)82002-0. ISBN 978-0-12-182786-1. PMID 15047094.
- ^ Crofts AR (2004). "The cytochrome bc1 complex: function in the context of structure". Annu. Rev. Physiol. 66: 689–733. doi:10.1146/annurev.physiol.66.032102.150251. PMID 14977419.
- ^ Ferguson SJ, Nicholls D, Ferguson S (2002). Bioenergetics (3rd ed.). San Diego: Academic. pp. 114–117. ISBN 978-0-12-518121-1.
- ^ Holmes, J. H.; Sapeika, N; Zwarenstein, H (1975). "Inhibitory effect of anti-obesity drugs on NADH dehydrogenase of mouse heart homogenates". Research Communications in Chemical Pathology and Pharmacology. 11 (4): 645–6. PMID 241101.
- ^ Muller, F. L.; Lustgarten, M. S.; Jang, Y.; Richardson, A. & Van Remmen, H. (2007). "Trends in oxidative aging theories". Free Radic. Biol. Med. 43 (4): 477–503. doi:10.1016/j.freeradbiomed.2007.03.034. PMID 17640558.
- ^ Skulachev VP (May 1996). "Role of uncoupled and non-coupled oxidations in maintenance of safely low levels of oxygen and its one-electron reductants". Q. Rev. Biophys. 29 (2): 169–202. doi:10.1017/s0033583500005795. PMID 8870073.
- ^ a b Muller F (2000). "The nature and mechanism of superoxide production by the electron transport chain: Its relevance to aging". AGE. 23 (4): 227–253. doi:10.1007/s11357-000-0022-9. PMC 3455268. PMID 23604868.
- ^ a b Muller FL, Liu Y, Van Remmen H (November 2004). "Complex III releases superoxide to both sides of the inner mitochondrial membrane". J. Biol. Chem. 279 (47): 49064–73. doi:10.1074/jbc.M407715200. PMID 15317809.
- ^ Han D, Williams E, Cadenas E (January 2001). "Mitochondrial respiratory chain-dependent generation of superoxide anion and its release into the intermembrane space". Biochem. J. 353 (Pt 2): 411–6. doi:10.1042/0264-6021:3530411. PMC 1221585. PMID 11139407.
- ^ DiMauro S (November 2006). "Mitochondrial myopathies" (PDF). Curr Opin Rheumatol. 18 (6): 636–41. doi:10.1097/01.bor.0000245729.17759.f2. PMID 17053512.
- ^ DiMauro S (June 2007). "Mitochondrial DNA medicine". Biosci. Rep. 27 (1–3): 5–9. doi:10.1007/s10540-007-9032-5. PMID 17484047.
- ^ Schuelke M, Krude H, Finckh B, Mayatepek E, Janssen A, Schmelz M, Trefz F, Trijbels F, Smeitink J (March 2002). "Septo-optic dysplasia associated with a new mitochondrial cytochrome b mutation". Ann. Neurol. 51 (3): 388–92. doi:10.1002/ana.10151. PMID 11891837.
- ^ Wibrand F, Ravn K, Schwartz M, Rosenberg T, Horn N, Vissing J (October 2001). "Multisystem disorder associated with a missense mutation in the mitochondrial cytochrome b gene". Ann. Neurol. 50 (4): 540–3. doi:10.1002/ana.1224. PMID 11601507.
- ^ Fisher N, Castleden CK, Bourges I, Brasseur G, Dujardin G, Meunier B (March 2004). "Human disease-related mutations in cytochrome b studied in yeast". J. Biol. Chem. 279 (13): 12951–8. doi:10.1074/jbc.M313866200. PMID 14718526.
Further reading
- Marres CM, Slater EC (1977). "Polypeptide composition of purified QH2:cytochrome c oxidoreductase from beef-heart mitochondria". Biochim. Biophys. Acta. 462 (3): 531–548. doi:10.1016/0005-2728(77)90099-8. PMID 597492.
- Rieske JS (1976). "Composition, structure, and function of complex III of the respiratory chain". Biochim. Biophys. Acta. 456 (2): 195–247. doi:10.1016/0304-4173(76)90012-4. PMID 788795.
- Wikstrom M, Krab K, Saraste M (1981). "Proton-translocating cytochrome complexes". Annu. Rev. Biochem. 50: 623–655. doi:10.1146/annurev.bi.50.070181.003203. PMID 6267990.
External links
- cytochrome bc1 complex site (Edward A. Berry) at the Wayback Machine (archived October 9, 2006) at lbl.gov
- cytochrome bc1 complex site (Antony R. Crofts) at uiuc.edu
- PROMISE Database: cytochrome bc1 complex at Archive.today (archived August 27, 1999) at scripps.edu
- Interactive Molecular Model of Complex III at the Wayback Machine (archived January 12, 2009) (Requires MDL Chime)
- UMich Orientation of Proteins in Membranes families/superfamily-3 - Calculated positions of bc1 and related complexes in membranes
- Coenzyme+Q-Cytochrome-c+Reductase at the US National Library of Medicine Medical Subject Headings (MeSH)
This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.
This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.
Ubiquinol-cytochrome C reductase complex 14kD subunit Provide feedback
The ubiquinol-cytochrome C reductase complex (cytochrome bc1 complex) is a respiratory multienzyme complex [1]. This Pfam family represents the 14kD (or VI) subunit of the complex which is not directly involved in electron transfer, but has a role in assembly of the complex [2].
Literature references
-
Iwata S, Lee JW, Okada K, Lee JK, Iwata M, Rasmussen B, Link TA, Ramaswamy S, Jap BK; , Science 1998;281:64-71.: Complete structure of the 11-subunit bovine mitochondrial cytochrome bc1 complex [see comments] PUBMED:9651245 EPMC:9651245
-
Braun HP, Schmitz UK; , Plant Physiol 1995;107:1217-1223.: Molecular features and mitochondrial import pathway of the 14-kilodalton subunit of cytochrome c reductase from potato. PUBMED:7770525 EPMC:7770525
External database links
SCOP: | 1bcc |
This tab holds annotation information from the InterPro database.
InterPro entry IPR003197
Cytochrome b-c1 complex subunit 7 (QCR7, also known as UQCRB) is a component of the ubiquinol-cytochrome c reductase complex (complex III or cytochrome b-c1 complex), which is part of the mitochondrial respiratory chain. QCR7 is involved in redox-linked proton pumping [PUBMED:2170131, PUBMED:6319130, PUBMED:11556808].
Gene Ontology
The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.
Cellular component | mitochondrial respiratory chain complex III (GO:0005750) |
Biological process | mitochondrial electron transport, ubiquinol to cytochrome c (GO:0006122) |
Domain organisation
Below is a listing of the unique domain organisations or architectures in which this domain is found. More...
Loading domain graphics...
Alignments
We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the UniProtKB sequence database, the NCBI sequence database, and our metagenomics sequence database. More...
View options
We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.
Seed (105) |
Full (1406) |
Representative proteomes | UniProt (2281) |
NCBI (2293) |
Meta (1) |
||||
---|---|---|---|---|---|---|---|---|---|
RP15 (218) |
RP35 (578) |
RP55 (930) |
RP75 (1324) |
||||||
Jalview | |||||||||
HTML | |||||||||
PP/heatmap | 1 |
1Cannot generate PP/Heatmap alignments for seeds; no PP data available
Key:
available,
not generated,
— not available.
Format an alignment
Download options
We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.
Seed (105) |
Full (1406) |
Representative proteomes | UniProt (2281) |
NCBI (2293) |
Meta (1) |
||||
---|---|---|---|---|---|---|---|---|---|
RP15 (218) |
RP35 (578) |
RP55 (930) |
RP75 (1324) |
||||||
Raw Stockholm | |||||||||
Gzipped |
You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.
HMM logo
HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...
Trees
This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.
Note: You can also download the data file for the tree.
Curation and family details
This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.
Curation
Seed source: | Pfam-B_4192 (release 5.2) |
Previous IDs: | none |
Type: | Family |
Sequence Ontology: | SO:0100021 |
Author: |
Mian N |
Number in seed: | 105 |
Number in full: | 1406 |
Average length of the domain: | 97.00 aa |
Average identity of full alignment: | 40 % |
Average coverage of the sequence by the domain: | 71.59 % |
HMM information
HMM build commands: |
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 47079205 -E 1000 --cpu 4 HMM pfamseq
|
||||||||||||
Model details: |
|
||||||||||||
Model length: | 100 | ||||||||||||
Family (HMM) version: | 17 | ||||||||||||
Download: | download the raw HMM for this family |
Species distribution
Sunburst controls
HideWeight segments by...
Change the size of the sunburst
Colour assignments
![]() |
![]() |
![]() |
![]() |
![]() |
![]() |
![]() |
![]() |
Selections
Align selected sequences to HMM
Generate a FASTA-format file
Clear selection
This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...
Tree controls
HideThe tree shows the occurrence of this domain across different species. More...
Loading...
Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.
Interactions
There are 10 interactions for this family. More...
Peptidase_M16 Peptidase_M16_C UCR_14kD UcrQ UcrQ Cytochrom_B_N_2 Cytochrom_B_C Cytochrom_C1 Peptidase_M16 Peptidase_M16_CStructures
For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the UCR_14kD domain has been found. There are 101 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein sequence.
Loading structure mapping...