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The semiquinone swing in the bifurcating electron transferring flavoprotein/butyryl-CoA dehydrogenase complex from Clostridium difficile

Demmer, Julius K., Pal Chowdhury, Nilanjan, Selmer, Thorsten, Ermler, Ulrich, Buckel, Wolfgang·2017·Nature Communications
DOI 10.1038/s41467-017-01746-3PMC PMC5691135
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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 the Clostridium 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. Superimposing Acidaminococcus fermentans EtfAB onto C. 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.

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Metadata

Authors
Demmer, J. K., Pal Chowdhury, N., Selmer, T., Ermler, U., & Buckel, W.
ORCID
Buckel, Wolfgang
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2017-11-17
Volume
8
Issue
1
ISSN
2041-1723
DOI
10.1038/s41467-017-01746-3
PMC
PMC5691135
Cited by
114
References
4
Language
en
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