The Crystal Structure of a Biological Insulated Transmembrane Molecular Wire

Edwards, Marcus J.; White, Gaye F.; Butt, Julea N.; Richardson, David J.; Clarke, Thomas A.

doi:10.1016/j.cell.2020.03.032

Cited by 144 publications

(180 citation statements)

References 53 publications

Supporting

Mentioning

170

Contrasting

Order By: Relevance

“…These results demonstrate the large conductance tunability of a molecular wire via tweaking its internal supramolecular interactions and present a novel platform to investigate the fascinating, yet unknown, field of the mechanobiology of electron transport in complex biomolecular structures. This porphyrin‐based supramolecular wire also brings a new synthetic testbench to study the molecular mechanisms supporting the exceedingly long‐range (from mesoscopic to micrometer range) charge transport in bacteria nanowires exploiting similar supramolecular interactions …”

Section: Resultsmentioning

confidence: 99%

Tuning Single‐Molecule Conductance in Metalloporphyrin‐Based Wires via Supramolecular Interactions

et al. 2020

View full text Add to dashboard Cite

Nature hasd eveloped supramolecular constructs to delivero utstanding charge-transport capabilities usingm etalloporphyrin-baseds upramoleculara rrays. Herein we incorporate simple,n aturally inspired supramolecular interactions via theaxial complexation of metalloporphyrinsintothe formation of as ingle-molecule wire in an anoscale gap. Smalls tructural changesi nt he axialc oordinatingl inkers result in dramatic changesi nt he transportp ropertieso ft he metalloporphyrinbasedw ire. Thei ncreased flexibilityo fapyridine-4-yl-methanethiol ligand duet oa ne xtra methyl group, as compared to am orer igid 4-pyridinethioll inker, allows thep yridine-4-ylmethanethiol ligand to adopta nu nexpectedh ighlyc onductive stackeds tructure betweent he twoj unctione lectrodesa nd the metalloporphyrin ring.D FT calculations reveal am olecular junction structurec omposedo fashifteds tack of thet wo pyridiniclinkers andthe metalloporphyrin ring.Incontrast, the more rigid4-mercaptopyridineligandpresentsamore classical lifted octahedral coordinationo ft he metalloporphyrin metal center,l eading to al ongere lectronp athway of lowerc onductance. This worksopens to supramolecular electronics, aconcept alreadyexploited in naturalorganisms.

show abstract

Section: Resultsmentioning

confidence: 99%

Tuning Single‐Molecule Conductance in Metalloporphyrin‐Based Wires via Supramolecular Interactions

et al. 2020

View full text Add to dashboard Cite

show abstract

“…Recently, multi-heme cytochromes (MHC) and their complexes have gained much attention due to their involvement in extracellular respiration and interspecies electron exchange in dissimilatory metal-reducing bacteria. 1 − 3 Atomic X-ray structures of several of these proteins were resolved for S. oneidensis , 4 − 8 and very recently also for G. sulfurreducens , 9 , 10 revealing closely packed heme c cofactor arrangements within the protein peptide matrices suggestive of their function as “biological nanowires”. MHC protein complexes 8 or polymers 9 , 10 span the entire bacterial envelope, thereby facilitating the export of electrons from the inside to the outside of the cell.…”

mentioning

confidence: 99%

“…1 − 3 Atomic X-ray structures of several of these proteins were resolved for S. oneidensis , 4 − 8 and very recently also for G. sulfurreducens , 9 , 10 revealing closely packed heme c cofactor arrangements within the protein peptide matrices suggestive of their function as “biological nanowires”. MHC protein complexes 8 or polymers 9 , 10 span the entire bacterial envelope, thereby facilitating the export of electrons from the inside to the outside of the cell. Experiments, 11 , 12 theory, 13 and computation 14 − 17 have given valuable insights into the thermodynamics, kinetics, and the mechanistic aspects of this process, in particular suggesting that electron transfer (ET) across these structures in their native (aqueous) environments occurs by consecutive heme-to-heme electron hopping.…”

mentioning

confidence: 99%

Coherent Electron Transport across a 3 nm Bioelectronic Junction Made of Multi-Heme Proteins

Futera

Ide

Kayser

et al. 2020

J. Phys. Chem. Lett.

Self Cite

View full text Add to dashboard Cite

Multi-heme cytochromes (MHCs) are fascinating proteins used by bacterial organisms to shuttle electrons within, between, and out of their cells. When placed in solid-state electronic junctions, MHCs support temperature-independent currents over several nanometers that are 3 orders of magnitude higher compared to other redox proteins of similar size. To gain molecular-level insight into their astonishingly high conductivities, we combine experimental photoemission spectroscopy with DFT+Σ current–voltage calculations on a representative Gold-MHC-Gold junction. We find that conduction across the dry, 3 nm long protein occurs via off-resonant coherent tunneling, mediated by a large number of protein valence-band orbitals that are strongly delocalized over heme and protein residues. This picture is profoundly different from the electron hopping mechanism induced electrochemically or photochemically under aqueous conditions. Our results imply that the current output in solid-state junctions can be even further increased in resonance, for example, by applying a gate voltage, thus allowing a quantum jump for next-generation bionanoelectronic devices.

show abstract

“…Although we hoped to gain clues on TprL function by conducting structural homology analyses, obtaining a consistent model for this protein remains an elusive task, as prediction softwares (Neff-MUSTER, SparksX, HHpred, and HHsearch, all form the LOMETS package) that identify structural homologs to TprL with a beta-barrel structure do not agree on any particular structural homolog. Predictions include electron transport proteins homologous to the Mtr complex of Shewanella baltica [47]; a Type 9 protein translocon homologous to the SprA protein of Flavobacterium johnsoniae [48] which however has a molecular mass three times that of TprL, OmpW of E. coli [49], which however is significantly smaller in size, and a green fluorescent protein of the hydromedusa Aqueora victoria. Further experimental work focusing on the analysis of this protein will shed light on its structure, and provide additional clues to its function and role in disease pathogenesis.…”

Section: Discussionmentioning

confidence: 99%

Transcriptional and immunological analysis of the putative outer membrane protein and vaccine candidate TprL ofTreponema pallidum

Haynes

Fernandez

Romeis

et al. 2020

Preprint

View full text Add to dashboard Cite

BackgroundAn effective syphilis vaccine should elicit antibodies to Treponema pallidum subsp. pallidum (T. p. pallidum) surface antigens to induce pathogen clearance through opsonophagocytosis. Although the combination of bioinformatics, structural, and functional analyses of T. p. pallidum genes to identify putative outer membrane proteins (OMPs) resulted in a list of potential vaccine candidates, still very little is known about whether and how transcription of these genes is regulated during infection. This knowledge gap is a limitation to vaccine design, as immunity generated to an antigen that can be down-regulated or even silenced at the transcriptional level without affecting virulence would not induce clearance of the pathogen, hence allowing disease progression.Principal findingsWe report here that tp1031, the T. p. pallidum gene encoding the putative OMP and vaccine candidate TprL is differentially expressed in several T. p. pallidum strains, suggesting transcriptional regulation. Experimental identification of the tprL transcriptional start site revealed that a homopolymeric G sequence of varying length resides within the tprL promoter and that its length affects promoter activity compatible with phase variation. Conversely, in the closely related pathogen T. p. subsp. pertenue, the agent of yaws, where a naturally-occurring deletion has eliminated the tprL promoter region, elements necessary for protein synthesis, and part of the gene ORF, tprL transcription level are negligible compared to T. p. pallidum strains. Accordingly, the humoral response to TprL is absent in yaws-infected laboratory animals and patients compared to syphilis-infected subjects.ConclusionThe ability of T. p. pallidum to stochastically vary tprL expression should be considered in any vaccine development effort that includes this antigen. The role of phase variation in contributing to T. p. pallidum antigenic diversity should be further studied.Author SummarySyphilis is still an endemic disease in many low- and middle-income countries and has been resurgent in high-income nations for almost two decades now. In endemic areas, syphilis still causes significant morbidity and mortality in patients, particularly when its causative agent, the bacterium Treponema pallidum subsp. pallidum is transmitted to the fetus during pregnancy. Although there are significant ongoing efforts to identify an effective syphilis vaccine to bring into clinical trials within the decade in the U.S., such efforts are partially hindered by the lack of knowledge on transcriptional regulation of many genes encoding vaccine candidates. Here, we start addressing this knowledge gap for the putative outer membrane protein (OMP) and vaccine candidates TprL, encoded by the tp1031 gene. As we previously reported for other putative OMP-encoding genes of the syphilis agent, tprL transcription level appears to be affected by the length of a homopolymeric sequence of guanosines (Gs) located within the gene promoter. This is a mechanism known as phase variation and often involved in altering the surface antigenic profile of a bacterial pathogen to facilitate immune evasion and/or adaptation to the host milieu.

show abstract

The Crystal Structure of a Biological Insulated Transmembrane Molecular Wire

Cited by 144 publications

References 53 publications

Tuning Single‐Molecule Conductance in Metalloporphyrin‐Based Wires via Supramolecular Interactions

Tuning Single‐Molecule Conductance in Metalloporphyrin‐Based Wires via Supramolecular Interactions

Coherent Electron Transport across a 3 nm Bioelectronic Junction Made of Multi-Heme Proteins

Transcriptional and immunological analysis of the putative outer membrane protein and vaccine candidate TprL ofTreponema pallidum

Contact Info

Product

Resources

About