Abstract
Certain dissimilatory bacteria have the remarkable ability to use extracellular metal oxide minerals instead of oxygen as terminal electron sinks, using a process known as “extracellular respiration”. Specialized multiheme cytochromes located on the outer membrane of the microbe were shown to be crucial for electron transfer from the cell surface to the mineral. This process is facilitated by soluble, biogenic flavins secreted by the organism for the purpose of acting as an electron shuttle. However, their interactions with the outer-membrane cytochromes are not established on a molecular scale. Here, we study the interaction between the outer-membrane deca-heme cytochrome MtrC from Shewanella oneidensis and flavin mononucleotide (FMN in fully oxidized quinone form) using computational docking. We find that interaction of FMN with MtrC is significantly weaker than with known FMN-binding proteins, but identify a mildly preferred interaction site close to heme 2 with a dissociation constant (Kd) = 490 μM, in good agreement with recent experimental estimates, Kd = 255 μM. The weak interaction with MtrC can be qualitatively explained by the smaller number of hydrogen bonds that the planar headgroup of FMN can form with this protein compared to FMN-binding proteins. Molecular dynamics simulation gives indications for a possible conformational switch upon cleavage of the disulphide bond of MtrC, but without concomitant increase in binding affinities according to this docking study. Overall, our results suggest that binding of FMN to MtrC is reversible and not highly specific, which may be consistent with a role as redox shuttle that facilitates extracellular respiration.
Highlights
Dissimilatory metal-reducing bacteria like Shewanella oneidensis possess the remarkable ability to utilize solid, extracellular metal oxides as terminal electron acceptors in place of oxygen
The best docking pose in the vicinity of heme 2 gives a dissociation constant Kd 1⁄4 490 mM, in very good agreement with the experimentally determined value, 255 mM [14]. This is orders-of-magnitude higher than for typical flavin mononucleotide (FMN)-binding proteins and supports the view that binding to MtrC is rather weak. This is traced back to the fewer number of hydrogen bonds that the headgroup of FMN can form with MtrC compared to FMN-binding proteins
At first we validated the blind docking protocol used by redocking of FMN to two flavin-binding proteins and found that both the experimental structures of the FMN-protein complexes as well as the binding affinities could be reproduced in very good agreement with experiment
Summary
Dissimilatory metal-reducing bacteria like Shewanella oneidensis possess the remarkable ability to utilize solid, extracellular metal oxides as terminal electron acceptors in place of oxygen. This unusual respiratory ability is facilitated by extracellular electron transfer (EET) between multiheme c-type cytochromes, located on the outer membrane (OM) of these bacteria (OM cytochromes) [1,2], and the metal oxide (see [3,41] for recent reviews). EET can take place directly at the cell surface or via micrometer-long conductive appendages, often termed ‘‘bacterial nanowires’’ The latter have been recently shown to be OM cytochrome-containing extensions of the outer membrane [6]. The relative physiological importance of these different mechanisms, direct versus shuttle and cell surface versus appendage-mediated, is still unclear
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