Electron flow in multiheme bacterial cytochromes is a balancing act between heme electronic interaction and redox potentials

Abstract

The naturally widespread process of electron transfer from metal reducing bacteria to extracellular solid metal oxides entails unique biomolecular machinery optimized for long-range electron transport. To perform this function efficiently, microorganisms have adapted multiheme c-type cytochromes to arrange heme cofactors into wires that cooperatively span the cellular envelope, transmitting electrons along distances greater than 100 Å. Implications and opportunities for bionanotechnological device design are selfevident. However, at the molecular level, how these proteins shuttle electrons along their heme wires, navigating intraprotein intersections and interprotein interfaces efficiently, remains a mystery thus far inaccessible to experiment. To shed light on this critical topic, we carried out extensive quantum mechanics/molecular mechanics simulations to calculate stepwise heme-to-heme electron transfer rates in the recently crystallized outer membrane deca-heme cytochrome MtrF. By solving a master equation for electron hopping, we estimate an intrinsic, maximum possible electron flux through solvated MtrF of 10 4 -10 5 s −1 , consistent with recently measured rates for the related multiheme protein complex MtrCAB. Intriguingly, our calculations show that the rapid electron transport through MtrF is the result of a clear correlation between heme redox potential and the strength of electronic coupling along the wire: thermodynamically uphill steps occur only between electronically well-connected stacked heme pairs. This observation suggests that the protein evolved to harbor low-potential hemes without slowing down electron flow. These findings are particularly profound in light of the apparently well-conserved staggered cross-heme wire structural motif in functionally related outer membrane proteins.respiration | density functional theory

Biological charge transfer via flickering resonance

“…Indeed, the sensitivity of biological electrontransfer (ET) rates to conformational fluctuations and consequent (transient) delocalization is the topic of intense interest (1)(2)(3). Resonant enhancement of biological ET rates is consistent with a growing body of physical and structural data found in DNA ET through stacked nucleobases (4), extended delocalized structures of bacterial photosynthesis (including the special pair, bridging chlorophyll and pheophytin) (5), the polaronic states of oxidized porphyrin arrays up to seven porphyrin diameters in spatial extent (6), micrometer-scale bacterial nanowires (7,8), multiheme oxidoreductases (9,10), amino acid side chains in ribonucleotide reductase (11), engineered protein-based hopping-chains (12), and centimeter-scale charge-transport chains in filamentous bacteria (13). Here, we describe a transient or flickering resonance (FR) mechanism for ET.…”

Multi-haem cytochromes inShewanella oneidensisMR-1: structures, functions and opportunities

“…These orbitals are typically highly anisotropic. Hence, the overlap and coupling are highly sensitive on the orientation of donor and acceptor [115]. (It remains unclear also what the effective packing density should be for close cofactor contacts: for the haem pair in cytochrome c oxidase with an edge-to-edge distance of ca 7 Å , a packing density reduced by a third was suggested [105].)…”

Proton Transport in the Outer‐Membrane Flavocytochrome Complex Limits the Rate of Extracellular Electron Transport

“…The in vivo EET rate per OM Cyt  c complex is at least 10‐fold lower (10 2 –10 3  electrons s −1 ) than that in a purified system 13. Given that the electron‐transport rate in a purified system is nearly equal to the theoretical value estimated from the interheme distance in the crystal structure of MtrF14 and based on an interheme electron‐hopping model15 (ca. 10 4  electrons s −1 ), the lower EET rate that was observed in vivo for the MR‐1 strain may be attributable to the slower removal of protons from the periplasm.…”