Kinetics of trifurcated electron flow in the decaheme bacterial proteins MtrC and MtrF

Abstract

The bacterium Shewanella oneidensis has evolved a sophisticated electron transfer (ET) machinery to export electrons from the cytosol to extracellular space during extracellular respiration. At the heart of this process are decaheme proteins of the Mtr pathway, MtrC and MtrF, located at the external face of the outer bacterial membrane. Crystal structures have revealed that these proteins bind 10 c-type hemes arranged in the peculiar shape of a staggered cross that trifurcates the electron flow, presumably to reduce extracellular substrates while directing electrons to neighboring multiheme cytochromes at either side along the membrane. Especially intriguing is the design of the heme junctions trifurcating the electron flow: they are made of coplanar and T-shaped heme pair motifs with relatively large and seemingly unfavorable tunneling distances. Here, we use electronic structure calculations and molecular simulations to show that the side chains of the heme rings, in particular the cysteine linkages inserting in the space between coplanar and T-shaped heme pairs, strongly enhance electronic coupling in these two motifs. This results in an ≈103-fold speedup of ET steps at heme junctions that would otherwise be rate limiting. The predicted maximum electron flux through the solvated proteins is remarkably similar for all possible flow directions, suggesting that MtrC and MtrF shuttle electrons with similar efficiency and reversibly in directions parallel and orthogonal to the outer membrane. No major differences in the ET properties of MtrC and MtrF are found, implying that the different expression levels of the two proteins during extracellular respiration are not related to redox function.

Electrocatalytic Properties of Immobilized Heme Proteins: Basic Principles and Applications

“…[78][79][80][81] In the latter case, the heme group can be removed easily from the protein by unfolding. [86][87][88][89][90] These peculiar ET properties raised much interest on these species for applications in mediatorless biofuel cells, electrosynthesis, bioelectronic junctions and devices. The large interest in this family of proteins arises from the possibility of having different oxidation states, peculiar spectroscopic properties, direct or inducible catalytic capacities, and very different physiological functions.…”

Ergodicity Breaking in Thermal Biological Electron Transfer? Cytochrome C Revisited II

“…What becomes clear from many simulation studies in our group is that the effect of electronic polarization of the environment (here protein and water) needs to be included in the calculations. 1,17,[44][45][46][47][48][49][50][51] Otherwise reorganization free energy is strongly overestimated compared to experimentally determined values from photoemission spectroscopy and electrochemistry, not only for proteins but also for simple aqueous transition metal ion complexes Ru(bpy)…”

Cryo-EM structures of the air-oxidized and dithionite-reduced photosynthetic alternative complex III from Roseiflexus castenholzii

“…The spatial organization of heme_2 to heme_5 resembles that of the tetraheme in Shewanella oneidensis STC, in which the electron transfer between stacked heme pairs is approximately an order of magnitude greater than for the T-shaped heme pairs ( 25 ). But the electronic coupling of T-shaped heme pairs would be strongly enhanced by cysteine linkages inserted in the space between these pairs ( 26 ). The heme_1 is closest in terms of edge-to-edge distance to [3Fe-4S] (8.3 Å), and it is buried in a hydrophobic pocket formed by residues from ActB, ActC, ActD, and ActE (fig.…”