Electron transfer pathways in a multiheme cytochrome MtrF

Abstract

In MtrF, an outer-membrane multiheme cytochrome, the 10 heme groups are arranged in heme binding domains II and IV along the pseudo-C 2 axis, forming the electron transfer (ET) pathways. Previous reports based on molecular dynamics simulations showed that the redox potential (E m ) values for the heme pairs located in symmetrical positions in domains II and IV were similar, forming bidirectional ET pathways [Breuer M, Zarzycki P, Blumberger J, Rosso KM (2012) J Am Chem Soc 134(24):9868-9871]. Here, we present the E m values of the 10 hemes in MtrF, solving the linear Poisson-Boltzmann equation and considering the protonation states of all titratable residues and heme propionic groups. In contrast to previous studies, the E m values indicated that the ET is more likely to be downhill from domain IV to II because of localization of acidic residues in domain IV. Reduction of hemes in MtrF lowered the E m values, resulting in switching to alternative downhill ET pathways that extended to the flavin binding sites. These findings present an explanation of how MtrF serves as an electron donor to extracellular substrates.decaheme | dissimilatory metal-reducing bacteria | flavin | Shewanella species | Mtr conduit

Distinct Electron Conductance Regimes in Bacterial Decaheme Cytochromes

“…[19][20][21] Blumberger and co-workers considered the case of as ingle electron hopping through the system;t hat is,a ssuming only one heme is reduced at atime. [21] In both studies,t he computed redox potentials required empirical shifts to account for the energetics of the actual ionization process which requires explicit electronic structure calculation: À1.567 eV [19] and À0.22 eV [21] added to the half-redox free energy for heme-c in solution. [21] In both studies,t he computed redox potentials required empirical shifts to account for the energetics of the actual ionization process which requires explicit electronic structure calculation: À1.567 eV [19] and À0.22 eV [21] added to the half-redox free energy for heme-c in solution.…”

“…[21] In both studies,t he computed redox potentials required empirical shifts to account for the energetics of the actual ionization process which requires explicit electronic structure calculation: À1.567 eV [19] and À0.22 eV [21] added to the half-redox free energy for heme-c in solution. [21] While shifting the computed potentials by the same value has no effect on the differences of the redox potentials between the hemes,t he empirical shifts make it difficult to elucidate the central detail of the free-energy landscape,which governs the ET mechanism, that is,w hat is the most likely overall oxidation state of the entire system. [21] While shifting the computed potentials by the same value has no effect on the differences of the redox potentials between the hemes,t he empirical shifts make it difficult to elucidate the central detail of the free-energy landscape,which governs the ET mechanism, that is,w hat is the most likely overall oxidation state of the entire system.…”

“…Previous theoretical studies focused on ET in MtrF. [19][20][21] Blumberger and co-workers considered the case of as ingle electron hopping through the system;t hat is,a ssuming only one heme is reduced at atime. [19,20,22] Ishikita and co-workers took astep further and considered ahole-hopping mechanism where as ingle heme is oxidized at at ime and the rest are reduced.…”

“…[19,20,22] Ishikita and co-workers took astep further and considered ahole-hopping mechanism where as ingle heme is oxidized at at ime and the rest are reduced. [21] In both studies,t he computed redox potentials required empirical shifts to account for the energetics of the actual ionization process which requires explicit electronic structure calculation: À1.567 eV [19] and À0.22 eV [21] added to the half-redox free energy for heme-c in solution. Thet wo studies report distinctly different free-energy landscapes:one shows apath with very low driving force between the terminal hemes, [19] whereas the other shows aclear downhill process.…”

“…Thet wo studies report distinctly different free-energy landscapes:one shows apath with very low driving force between the terminal hemes, [19] whereas the other shows aclear downhill process. [21] While shifting the computed potentials by the same value has no effect on the differences of the redox potentials between the hemes,t he empirical shifts make it difficult to elucidate the central detail of the free-energy landscape,which governs the ET mechanism, that is,w hat is the most likely overall oxidation state of the entire system.…”