The semiquinone swing in the bifurcating electron transferring flavoprotein/butyryl-CoA dehydrogenase complex from Clostridium difficile. Issue 1 (December 2017)

• Record Type: Journal Article
• Authors: Demmer, Julius; Pal Chowdhury, Nilanjan; Selmer, Thorsten; Ermler, Ulrich; Buckel, Wolfgang
• Is Part Of: Nature communications. Volume 8:Issue 1(2017)
• Page Start: 1
• Page End: 10
• Publication Date: 2017-12
• Subjects: Biology -- Periodicals; Physical sciences -- Periodicals; 505
• DOI: 10.1038/s41467-017-01746-3
• Languages: English
• ISSNs: 2041-1723

Abstract

Abstract The electron transferring flavoprotein/butyryl-CoA dehydrogenase (EtfAB/Bcd) catalyzes the reduction of one crotonyl-CoA and two ferredoxins by two NADH within a flavin-based electron-bifurcating process. Here we report on the X-ray structure of theClostridium difficile (EtfAB/Bcd)4 complex in the dehydrogenase-conducting D-state, α-FAD (bound to domain II of EtfA) and δ-FAD (bound to Bcd) being 8 Å apart. SuperimposingAcidaminococcus fermentans EtfAB ontoC. difficile EtfAB/Bcd reveals a rotation of domain II of nearly 80°. Further rotation by 10° brings EtfAB into the bifurcating B-state, α-FAD and β-FAD (bound to EtfB) being 14 Å apart. This dual binding mode of domain II, substantiated by mutational studies, resembles findings in non-bifurcating EtfAB/acyl-CoA dehydrogenase complexes. In our proposed mechanism, NADH reduces β-FAD, which bifurcates. One electron goes to ferredoxin and one to α-FAD, which swings over to reduce δ-FAD to the semiquinone. Repetition affords a second reduced ferredoxin and δ-FADH−, which reduces crotonyl-CoA. The electron-transferring flavoprotein / butyryl-CoA dehydrogenase (EtfAB/Bcd) complex catalyzes the reduction of crotonyl-CoA and ferredoxins by NADH in anaerobic microbes. Here, the authors present the crystal structure ofClostridium difficile EtfAB/Bcd and discuss the bifurcation mechanism for electron flow.