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Binding of the Covalent Flavin Assembly Factor to the Flavoprotein Subunit of Complex II.


AUTHORS

Maklashina E , Rajagukguk S , Starbird CA , McDonald WH , Koganitsky A , Eisenbach M , Iverson TM , Cecchini G , . The Journal of biological chemistry. 2015 12 7; ().

ABSTRACT

Escherichia coli harbors two highly conserved homologs of the essential mitochondrial respiratory complex II (succinate:ubiquinone oxidoreductase, SQR). Aerobically the bacterium synthesizes SQR as part of its respiratory chain whereas under microaerophilic conditions the quinol:fumarate reductase (QFR) can be utilized. All complex II enzymes harbor a covalently bound FAD cofactor that is essential for their ability to oxidize succinate. In eukaryotes and many bacteria, assembly of the covalent flavin linkage is facilitated by a small protein assembly factor, termed SdhE in E. coli. How SdhE assists with formation of the covalent flavin bond or how it binds the flavoprotein subunit of complex II remains unknown. Using photocrosslinking we report the interaction site between the flavoprotein of complex II and the SdhE assembly factor. These data indicate that SdhE binds to the flavoprotein between two independently folded domains and that this binding mode likely influences the interdomain orientation. In so doing, SdhE likely orients amino acid residues near the dicarboxylate and FAD binding site which facilitates formation of the covalent flavin linkage. These studies identify how the conserved SdhE assembly factor and its homologs participate in complex II maturation.


Escherichia coli harbors two highly conserved homologs of the essential mitochondrial respiratory complex II (succinate:ubiquinone oxidoreductase, SQR). Aerobically the bacterium synthesizes SQR as part of its respiratory chain whereas under microaerophilic conditions the quinol:fumarate reductase (QFR) can be utilized. All complex II enzymes harbor a covalently bound FAD cofactor that is essential for their ability to oxidize succinate. In eukaryotes and many bacteria, assembly of the covalent flavin linkage is facilitated by a small protein assembly factor, termed SdhE in E. coli. How SdhE assists with formation of the covalent flavin bond or how it binds the flavoprotein subunit of complex II remains unknown. Using photocrosslinking we report the interaction site between the flavoprotein of complex II and the SdhE assembly factor. These data indicate that SdhE binds to the flavoprotein between two independently folded domains and that this binding mode likely influences the interdomain orientation. In so doing, SdhE likely orients amino acid residues near the dicarboxylate and FAD binding site which facilitates formation of the covalent flavin linkage. These studies identify how the conserved SdhE assembly factor and its homologs participate in complex II maturation.