Electron Transfer Flavoprotein
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An electron transfer flavoprotein (ETF) or electron transfer flavoprotein complex (CETF) is a
flavoprotein Flavoproteins are proteins that contain a nucleic acid derivative of riboflavin. These proteins are involved in a wide array of biological processes, including removal of radicals contributing to oxidative stress, photosynthesis, and DNA repair. ...
located on the matrix face of the inner mitochondrial membrane and functions as a specific electron acceptor for primary
dehydrogenase A dehydrogenase is an enzyme belonging to the group of oxidoreductases that oxidizes a substrate by reducing an electron acceptor, usually NAD+/NADP+ or a flavin coenzyme such as FAD or FMN. Like all catalysts, they catalyze reverse as well as ...
s, transferring the electrons to terminal respiratory systems such as
electron-transferring-flavoprotein dehydrogenase Electron-transferring-flavoprotein dehydrogenase (''ETF dehydrogenase'' or ''electron transfer flavoprotein-ubiquinone oxidoreductase'', ) is an enzyme that transfers electrons from electron-transferring flavoprotein in the mitochondrial matrix, ...
. They can be functionally classified into constitutive, "housekeeping" ETFs, mainly involved in the oxidation of
fatty acids In chemistry, in particular in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, ...
(Group I), and ETFs produced by some prokaryotes under specific growth conditions, receiving electrons only from the oxidation of specific substrates (Group II). ETFs are
heterodimeric In biochemistry, a protein dimer is a macromolecular complex or multimer formed by two protein monomers, or single proteins, which are usually non-covalently bound. Many macromolecules, such as proteins or nucleic acids, form dimers. The word ...
proteins composed of an alpha and beta subunit ( ETFA and ETFB), and contain an
FAD A fad, trend, or craze is any form of collective behavior that develops within a culture, a generation, or social group in which a group of people enthusiastically follow an impulse for a short time period. Fads are objects or behaviors tha ...
cofactor and
AMP Amp or AMP may refer to: * Ampere, a unit of electric current, often shortened to amp * Amplifier, a device that increases the amplitude of a signal Arts and entertainment Music * After Midnight Project, Los Angeles alternative rock band * A ...
. ETF consists of three domains: domains I and II are formed by the N- and C-terminal portions of the alpha subunit, respectively, while domain III is formed by the beta subunit. Domains I and III share an almost identical alpha-beta-alpha sandwich fold, while domain II forms an alpha-beta-alpha sandwich similar to that of bacterial
flavodoxin Flavodoxins (Fld) are small, soluble electron-transfer proteins. Flavodoxins contains flavin mononucleotide as prosthetic group. The structure of flavodoxin is characterized by a five-stranded parallel beta sheet, surrounded by five alpha helices. ...
s. FAD is bound in a cleft between domains II and III, while domain III binds the AMP molecule. Interactions between domains I and III stabilise the protein, forming a shallow bowl where domain II resides. LYRM5, a member of the
LYRM protein Leu-Tyr-Arg motif-containing proteins (LYRMs) form a superfamily of small (<15), positively charged and predominantly
superfamily SUPERFAMILY is a database and search platform of structural and functional annotation for all proteins and genomes. It classifies amino acid sequences into known structural domains, especially into SCOP superfamilies. Domains are functional, str ...
, interacts with ETFA and ETFB in a manner that deflavonates ETF by destabilizing the FAD binding site, leading to FAD release and thus disruption of
electron transfer Electron transfer (ET) occurs when an electron relocates from an atom, ion, or molecule, to another such chemical entity. ET describes the mechanism by which electrons are transferred in redox reactions. Electrochemical processes are ET reactio ...
. Mutation in ETFs can lead to deficiency of passing reducing equivalent of FADH2 to electron transport chain, causing
Glutaric acidemia type 2 Glutaric acidemia type 2 is an autosomal recessive metabolic disorder that is characterised by defects in the ability of the body to use proteins and fats for energy. Incompletely processed proteins and fats can build up, leading to a dangerous ch ...


See also

*
Electron transport chain An electron transport chain (ETC) is a series of protein complexes and other molecules which transfer electrons from electron donors to electron acceptors via redox reactions (both reduction and oxidation occurring simultaneously) and couples th ...
*
Electron-transferring-flavoprotein dehydrogenase Electron-transferring-flavoprotein dehydrogenase (''ETF dehydrogenase'' or ''electron transfer flavoprotein-ubiquinone oxidoreductase'', ) is an enzyme that transfers electrons from electron-transferring flavoprotein in the mitochondrial matrix, ...
*
Glutaric acidemia type 2 Glutaric acidemia type 2 is an autosomal recessive metabolic disorder that is characterised by defects in the ability of the body to use proteins and fats for energy. Incompletely processed proteins and fats can build up, leading to a dangerous ch ...
*
Metabolism Metabolism (, from ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cellular processes; the co ...
*
Microbial metabolism Microbial metabolism is the means by which a microbe obtains the energy and nutrients (e.g. carbon) it needs to live and reproduce. Microbes use many different types of metabolic strategies and species can often be differentiated from each other ...
*
Oxidative phosphorylation Oxidative phosphorylation(UK , US : or electron transport-linked phosphorylation or terminal oxidation, is the metabolic pathway in which Cell (biology), cells use enzymes to Redox, oxidize nutrients, thereby releasing chemical energy in order ...


References

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External links


Pfam entry for Electron transfer flavoprotein domain

Pfam entry for Electron transfer flavoprotein FAD-binding domain
Proteins