Taxonomic distribution of proteins containing ETF domains

The tree below includes only several representative species and genera. The complete taxonomic breakdown of all proteins containing ETF domains can be accessed here. Click the counts or percentage values to display the corresponding proteins.

Three-dimensional structure of human electron transfer flavoprotein to2.1-A resolution.

Roberts DL, Frerman FE, Kim JJ
Proc Natl Acad Sci U S A. 1996; 93: 14355-60

Mammalian electron transfer flavoproteins (ETF) are heterodimerscontaining a single equivalent of flavin adenine dinucleotide (FAD). Theyfunction as electron shuttles between primary flavoprotein dehydrogenasesinvolved in mitochondrial fatty acid and amino acid catabolism and themembrane-bound electron transfer flavoprotein ubiquinone oxidoreductase.The structure of human ETF solved to 2.1-A resolution reveals that the ETFmolecule is comprised of three distinct domains: two domains arecontributed by the alpha subunit and the third domain is made up entirelyby the beta subunit. The N-terminal portion of the alpha subunit and themajority of the beta subunit have identical polypeptide folds, in theabsence of any sequence homology. FAD lies in a cleft between the twosubunits, with most of the FAD molecule residing in the C-terminal portionof the alpha subunit. Alignment of all the known sequences for the ETFalpha subunits together with the putative FixB gene product shows that theresidues directly involved in FAD binding are conserved. A hydrogen bondis formed between the N5 of the FAD isoalloxazine ring and the hydroxylside chain of alpha T266, suggesting why the pathogenic mutation, alphaT266M, affects ETF activity in patients with glutaric acidemia type II.Hydrogen bonds between the 4'-hydroxyl of the ribityl chain of FAD and N1of the isoalloxazine ring, and between alpha H286 and the C2-carbonyloxygen of the isoalloxazine ring, may play a role in the stabilization ofthe anionic semiquinone. With the known structure of medium chain acyl-CoAdehydrogenase, we hypothesize a possible structure for docking the twoproteins.

Bradyrhizobium japonicum possesses two discrete sets of electron transferflavoprotein genes: fixA, fixB and etfS, etfL.

Weidenhaupt M, Rossi P, Beck C, Fischer HM, Hennecke H
Arch Microbiol. 1996; 165: 169-78

A group of four co-regulated genes (fixA, fixB, fixC, fixX) essential forsymbiotic nitrogen fixation has been described in several rhizobialspecies, including Bradyrhizobium japonicum. The complete nucleotidesequence of the B. japonicum fixA, fixB and fixC, genes is reported here.The derived amino acid sequences confirmed the previously noted sequencesimilarity between FixA and the beta-subunit and between FixB and thealpha-subunit of mammalian and Paracoccus denitrificans electron transferflavoproteins (ETF). Since the classical role of ETF is in beta-oxidationof fatty acids, a process unrelated to nitrogen fixation, we rationalizedthat B. japonicum ought to contain bona fide etf genes in addition to theetf-like genes fixA and fixB. Therefore, we identified, cloned, sequenced,and transcriptionally analyzed the B. japonicum etfSL genes encoding thebeta- and alpha-subunits of ETF. The etfSL genes, but not the fix genes,are transcribed in aerobically grown cells. An amino acid sequencecomparison between all available ETFs and ETF-like proteins revealed theexistence of two distinguishable subfamilies. Group I compriseshousekeeping ETFs that link acyl-CoA dehydrogenase reactions with therespiratory chain, such as in the fatty acid degradation pathway. B.japonicum EtfS and EtfL clearly belong to this group. Group II containsETF-like proteins that are synthesized only under certain specific growthconditions and receive electrons from the oxidation of specificsubstrates. The products of the anaerobically induced fixA and fixB genesof B. japonicum are members of that group. B. japonicum is the firstexample of an organism in which genes for proteins of both groups I and IIof the ETF family have been identified.