Structural insight on the mechanism of an electron-bifurcating [FeFe] hydrogenase
- University of York, United Kingdom
- Max Planck Institute for Chemical Energy Conversion, Germany
- Nara Institute of Science and Technology, Japan
Abstract
Electron-bifurcation is a fundamental energy conservation mechanism in nature in which two electrons from an intermediate potential electron donor are split so that one is sent along a high potential pathway to a high potential acceptor and the other is sent along a low potential pathway to a low potential acceptor. This process allows endergonic reactions to be driven by exergonic ones and is an alternative, less recognised, mechanism of energy coupling to the well-known chemiosmotic principle. The electron-bifurcating [FeFe] hydrogenase from Thermotoga maritima (HydABC) requires both NADH and ferredoxin to reduce protons generating hydrogen. The mechanism of electron-bifurcation in HydABC remains enigmatic in spite of intense research efforts over the last few years. Structural information may provide the basis for a better understanding of spectroscopic and functional information. Here, we present a 2.3 Å electron cryo-microscopy structure of HydABC. The structure shows a heterododecamer composed of two independent 'halves' each made of two strongly interacting HydABC heterotrimers connected via a [4Fe-4S] cluster. A central electron transfer pathway connects the active sites for NADH oxidation and for proton reduction. We identified two conformations of a flexible iron-sulfur cluster domain: a 'closed bridge' and an 'open bridge' conformation, where a Zn2+ site may act as a 'hinge' allowing domain movement. Based on these structural revelations, we propose a possible mechanism of electron-bifurcation in HydABC where the flavin mononucleotide serves a dual role as both the electron bifurcation center and as the NAD+ reduction/NADH oxidation site.
Data availability
Protein databank (PDB) files for the four model presented in this manuscript are available at https://www.rcsb.org/ under PDB ID 7P5H (D2 tetramer, 7P8N (Bridge closed forward), 7P91 (Bridge closed reverse), and 7P92 (Open bridge). Cryo-EM maps are available at https://www.ebi.ac.uk/pdbe/emdb/. All other data are available in the main text or the supplementary materials.
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Funding
Deutsche Forschungsgemeinschaft (BI 2198/1-1)
- Nipa Chongdar
- James A Birrell
UK Research and Innovation (MR/T040742/1)
- James N Blaza
Japan Society for the Promotion of Science (JP20H03215)
- Hideaki Ogata
Max-Planck-Gesellschaft (n/a)
- Nipa Chongdar
- Wolfgang Lubitz
- James A Birrell
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2022, Furlan et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Structural insight on the mechanism of an electron-bifurcating [FeFe] hydrogenase
eLife 11:e79361.
https://doi.org/10.7554/eLife.79361
