Abstract
Here we report the crystal structures of a ternary electron transfer complex showing extensive motion at the protein interface. This physiological complex comprises the iron-sulfur flavoprotein trimethylamine dehydrogenase and electron transferring flavoprotein (ETF) from Methylophilus methylotrophus. In addition, we report the crystal structure of free ETF. In the complex, electron density for the FAD domain of ETF is absent, indicating high mobility. Positions for the FAD domain are revealed by molecular dynamics simulation, consistent with crystal structures and kinetic data. A dual interaction of ETF with trimethylamine dehydrogenase provides for dynamical motion at the protein interface: one site acts as an anchor, thereby allowing the other site to sample a large range of interactions, some compatible with rapid electron transfer. This study establishes the role of conformational sampling in multi-domain redox systems, providing insight into electron transfer between ETFs and structurally distinct redox partners.
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Acknowledgements
The work was funded by the Biotechnology and Biological Sciences Research Council and the Lister Institute of Preventive Medicine. We thank C. Verma for useful discussions on the dynamics calculations. These were performed using the supercomputer at the University of Leicester Mathematical Modelling Centre, which was purchased through the EPSRC strategic equipment initiative. N.S.S. is a Lister Institute Research Professor. We gratefully acknowledge the use of beamlines at the DESY EMBL outstation, Hamburg, SRS Daresbury and at ESRF, Grenoble.
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Leys, D., Basran, J., Talfournier, F. et al. Extensive conformational sampling in a ternary electron transfer complex. Nat Struct Mol Biol 10, 219–225 (2003). https://doi.org/10.1038/nsb894
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DOI: https://doi.org/10.1038/nsb894
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