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1.
Artigo em Inglês | MEDLINE | ID: mdl-31961644

RESUMO

As a parent compound of Li-rich electrodes, Li2MnO3 exhibits high capacity during the initial charge; however, it suffers notoriously low Coulombic efficiency due to oxygen and surface activities. Here, we successfully optimize the oxygen activities toward reversible oxygen redox reactions by intentionally introducing protons into lithium octahedral vacancies in the Li2MnO3 system with its original structural integrity maintained. Combining structural probes, theoretical calculations, and resonant inelastic X-ray scattering results, a moderate coupling between the introduced protons and lattice oxygen at the oxidized state is revealed, which stabilizes the oxygen activities during charging. Such a coupling leads to an unprecedented initial Coulombic efficiency (99.2%) with a greatly improved discharge capacity of 302 mAh g-1 in the protonated Li2MnO3 electrodes. These findings directly demonstrate an effective concept for controlling oxygen activities in Li-rich systems, which is critical for developing high-energy cathodes in batteries.

2.
J Am Chem Soc ; 142(5): 2115-2119, 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31970982

RESUMO

The integral membrane M2 protein is a 97-residue membrane protein that assembles as a tetramer to conduct protons at a slow rate (102-103/s) when activated by low pH. The proton conductance mechanism has been extensively debated in the literature, but it is accepted that the proton conductance is facilitated by hydrogen bonds involving the His37 residues. However, the hydrogen bonding partnership remains unresolved. Here, we report on the measurement of 15N-15N J-couplings of 15N His37-labeled full length M2 (M2FL) protein from Influenza A virus embedded in synthetic liquid crystalline lipid bilayers using two-dimensional J-resolved NMR spectroscopy. We experimentally observed the hydrogen-bond mediated J-couplings between Nδ1 and Nε2 of adjacent His37 imidazole rings, providing direct evidence for the existence of various imidazolium-imidazole hydrogen-bonding geometries in the histidine tetrad at low pH, thus validating the proton conduction mechanism in the M2FL protein by which the proton is transferred through the breaking and reforming of the hydrogen bonds between pairs of His37 residues.

3.
J Magn Reson ; 310: 106639, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31734618

RESUMO

Membrane proteins perform many important cellular functions. Historically, structural studies of these proteins have been conducted in detergent preparations and synthetic lipid bilayers. More recently, magic-angle-spinning (MAS) solid-state NMR has been employed to analyze membrane proteins in native membrane environments, but resonance assignments with this technique remain challenging due to limited spectral resolution and high resonance degeneracy. To tackle this issue, we combine reverse labeling of amino acids, frequency-selective dipolar dephasing, and NMR difference spectroscopy. These methods have resulted in nearly complete resonance assignments of the transmembrane domain of human LR11 (SorLA) protein in E. coli membranes. To reduce background signals from E. coli lipids and proteins and improve spectral sensitivity, we effectively utilize amylose affinity chromatography to prepare membrane vesicles when MBP is included as a fusion partner in the expression construct.

4.
Chemphyschem ; 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31805217

RESUMO

We provide an experimental and computational framework for 2 H quadrupolar chemical exchange saturation transfer NMR experiments (Q-CEST) under static solid-state conditions for the quantification of dynamics on µs-ms timescales. Simulations using simple 2-site exchange models provide insights into the relation between spin dynamics and motions. Biological applications focus on two sites of amyloid-ß fibrils in the 3-fold symmetric polymorph. The first site, the methyl group of A2 of the disordered N-terminal domain, undergoes diffusive motions and conformational exchange due to transient interactions. Earlier 2 H rotating frame relaxation and quadrupolar CPMG measurements are combined with the Q-CEST approach to characterize the multiple conformational states of the domain. The second site, the methyl group of M35, spans the water-accessible cavity inside the fibrils' core and undergoes extensive rotameric exchange. Q-CEST permits us to refine the rotameric exchange model for this site and allows the more precise determination of populations and rotameric exchange rate constants than line shape analysis.

5.
J Biomol NMR ; 2019 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-31760571

RESUMO

Incorporation of 19F into proteins allows for the study of their molecular interactions via NMR. The study of 19F labeled aromatic amino acids has largely focused on 4-,5-, or 6-fluorotryptophan, 4-fluorophenylalanine, (4,5, or 6FW) or 3-fluorotyrosine (3FY), whereas 2-fluorotyrosine (2FY) has remained largely understudied. Here we report a comparative analysis with different fluorinated amino acids. We first report the NMR chemical shift responsiveness of five aromatic amino acid mimics to changes in solvent polarity and find that the most responsive, a mimic of 3FY, has a 2.9-fold greater change in chemical shift compared to the other amino acid mimics in aprotic solvents including the 2FY mimic. We also probed the utility of 2FY for 19F NMR by measuring its NMR relaxation properties in solution and the chemical shift anisotropy (CSA) of a polycrystalline sample of the amino acid by magic angle spinning. Using protein-observed fluorine NMR (PrOF NMR), we compared the influence of 2FY and 3FY incorporation on stability and pKa perturbation when incorporated into the KIX domain of CBP/p300. Lastly, we investigated the 19F NMR response of both 2FY and 3FY-labeled proteins to a protein-protein interaction partner, MLL, and discovered that 2FY can report on allosteric interactions that are not observed with 3FY-labeling in this protein complex. The reduced perturbation to pKa and similar but reduced CSA of 2FY to 3FY supports 2FY as a suitable alternative amino acid for incorporation into large proteins for 19F NMR analysis.

6.
J Biol Chem ; 294(49): 18557-18570, 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31619519

RESUMO

The host-defense peptide (HDP) piscidin 1 (P1), isolated from the mast cells of striped bass, has potent activities against bacteria, viruses, fungi, and cancer cells and can also modulate the activity of membrane receptors. Given its broad pharmacological potential, here we used several approaches to better understand its interactions with multicomponent bilayers representing models of bacterial (phosphatidylethanolamine (PE)/phosphatidylglycerol) and mammalian (phosphatidylcholine/cholesterol (PC/Chol)) membranes. Using solid-state NMR, we solved the structure of P1 bound to PC/Chol and compared it with that of P3, a less potent homolog. The comparison disclosed that although both peptides are interfacially bound and α-helical, they differ in bilayer orientations and depths of insertion, and these differences depend on bilayer composition. Although Chol is thought to make mammalian membranes less susceptible to HDP-mediated destabilization, we found that Chol does not affect the permeabilization effects of P1. X-ray diffraction experiments revealed that both piscidins produce a demixing effect in PC/Chol membranes by increasing the fraction of the Chol-depleted phase. Furthermore, P1 increased the temperature required for the lamellar-to-hexagonal phase transition in PE bilayers, suggesting that it imposes positive membrane curvature. Patch-clamp measurements on the inner Escherichia coli membrane showed that P1 and P3, at concentrations sufficient for antimicrobial activity, substantially decrease the activating tension for bacterial mechanosensitive channels. This indicated that piscidins can cause lipid redistribution and restructuring in the microenvironment near proteins. We conclude that the mechanism of piscidin's antimicrobial activity extends beyond simple membrane destabilization, helping to rationalize its broader spectrum of pharmacological effects.

7.
Biophys J ; 117(8): 1524-1535, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31570231

RESUMO

We investigate the variability in the dynamics of the disordered N-terminal domain of amyloid-ß fibrils (Aß), comprising residues 1-16 of Aß1-40, due to post-translational modifications and mutations in the ß-bend regions known to modulate aggregation properties. Using 2H static solid-state NMR approaches, we compare the dynamics in the wild-type Aß fibrils in the threefold symmetric polymorph with the fibrils from three post-translational modification sequences: isoaspartate-D7, the phosphorylation of S8, and an N-terminal truncation ΔE3. Additional comparisons are made with the mutants in the ß-bend region (residues 21-23) corresponding to the familial Osaka E22Δ deletion and D23N Iowa mutation. We also include the aggregates induced by Zn2+ ions. The dynamics are probed at the F4 and G9 positions. The main motional model involves two free states undergoing diffusion and conformational exchanges with the bound state in which the diffusion is quenched because of transient interactions involving fibril core and other intrastrand contacts. The fraction of the bound state increases in a sigmoidal fashion with a decrease in temperature. There is clear variability in the dynamics: the phosphorylation of S8 variant is the most rigid at the G9 site in line with structural studies, the ΔE3 fibrils are more flexible at the G9 site in line with the morphological fragmentation pattern, the Zn-induced aggregates are the most mobile, and the two ß-bend mutants have the strongest changes at the F4 site toward higher rigidity. Overall, the changes underlie the potential role of conformational ensembles in setting the stage for aggregation-prone states.

8.
Angew Chem Int Ed Engl ; 58(50): 18086-18095, 2019 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-31587462

RESUMO

Sodium layered P2-stacking Na0.67 MnO2 materials have shown great promise for sodium-ion batteries. However, the undesired Jahn-Teller effect of the Mn4+ /Mn3+ redox couple and multiple biphasic structural transitions during charge/discharge of the materials lead to anisotropic structure expansion and rapid capacity decay. Herein, by introducing abundant Al into the transition-metal layers to decrease the number of Mn3+ , we obtain the low cost pure P2-type Na0.67 Alx Mn1-x O2 (x=0.05, 0.1 and 0.2) materials with high structural stability and promising performance. The Al-doping effect on the long/short range structural evolutions and electrochemical performances is further investigated by combining in situ synchrotron XRD and solid-state NMR techniques. Our results reveal that Al-doping alleviates the phase transformations thus giving rise to better cycling life, and leads to a larger spacing of Na+ layer thus producing a remarkable rate capability of 96 mAh g-1 at 1200 mA g-1 .

9.
J Phys Chem B ; 123(38): 8034-8047, 2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31483653

RESUMO

Transmembrane domains of membrane proteins sometimes contain conserved charged or ionizable residues which may be essential for protein function and regulation. This work examines the molecular interactions of single Arg residues within a highly dynamic transmembrane peptide helix. To this end, we have modified the GW4,20ALP23 (acetyl-GGAW4(AL)7AW20AGA-amide) model peptide framework to incorporate Arg residues near the center of the peptide. Peptide helix formation, orientation and dynamics were analyzed by means of solid-state NMR spectroscopy to monitor specific 2H- or 15N-labeled residues. GW4,20ALP23 itself adopts a tilted orientation within lipid bilayer membranes. Nevertheless, the GW4,20ALP23 helix exhibits moderate to high dynamic averaging of NMR observables, such as 2H quadrupolar splittings or 15N-1H dipolar couplings, due to competition between the interfacial Trp residues on opposing helix faces. Here we examine how the helix dynamics are impacted by the introduction of a single Arg residue at position 12 or 14. Residue R14 restricts the helix to low dynamic averaging and a well-defined tilt that varies inversely with the lipid bilayer thickness. To compensate for the dominance of R14, the competing Trp residues cause partial unwinding of the helix at the C-terminal. By contrast, R12GW4,20ALP23 exits the DOPC bilayer to an interfacial surface-bound location. Interestingly, multiple orientations are exhibited by a single residue, Ala-9. Quadrupolar splittings generated by 2H-labeled residues A3, A5, A7, and A9 do not fit to the α-helical quadrupolar wave plot defined by residues A11, A13, A15, A17, A19, and A21. The discontinuity at residue A9 implicates a helical swivel distortion and an apparent 310-helix involving the N-terminal residues preceding A11. These molecular features suggest that, while arginine residues are prominent factors controlling transmembrane helix dynamics, the influence of interfacial tryptophan residues cannot be ignored.

10.
J Am Chem Soc ; 141(25): 9837-9853, 2019 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-31144503

RESUMO

Piscidins are histidine-enriched antimicrobial peptides that interact with lipid bilayers as amphipathic α-helices. Their activity at acidic and basic pH in vivo makes them promising templates for biomedical applications. This study focuses on p1 and p3, both 22-residue-long piscidins with 68% sequence identity. They share three histidines (H3, H4, and H11), but p1, which is significantly more permeabilizing, has a fourth histidine (H17). This study investigates how variations in amphipathic character associated with histidines affect the permeabilization properties of p1 and p3. First, we show that the permeabilization ability of p3, but not p1, is strongly inhibited at pH 6.0 when the conserved histidines are partially charged and H17 is predominantly neutral. Second, our neutron diffraction measurements performed at low water content and neutral pH indicate that the average conformation of p1 is highly tilted, with its C-terminus extending into the opposite leaflet. In contrast, p3 is surface bound with its N-terminal end tilted toward the bilayer interior. The deeper membrane insertion of p1 correlates with its behavior at full hydration: an enhanced ability to tilt, bury its histidines and C-terminus, induce membrane thinning and defects, and alter membrane conductance and viscoelastic properties. Furthermore, its pH-resiliency relates to the neutral state favored by H17. Overall, these results provide mechanistic insights into how differences in the histidine content and amphipathicity of peptides can elicit different directionality of membrane insertion and pH-dependent permeabilization. This work features complementary methods, including dye leakage assays, NMR-monitored titrations, X-ray and neutron diffraction, oriented CD, molecular dynamics, electrochemical impedance spectroscopy, surface plasmon resonance, and quartz crystal microbalance with dissipation.

11.
Molecules ; 24(10)2019 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-31126069

RESUMO

In 1953, Pauling and Corey predicted that enantiomeric ß-sheet peptides would coassemble into so-called "rippled" ß-sheets, in which the ß-sheets would consist of alternating l- and d-peptides. To date, this phenomenon has been investigated primarily with amphipathic peptide sequences composed of alternating hydrophilic and hydrophobic amino acid residues. Here, we show that enantiomers of a fragment of the amyloid-ß (Aß) peptide that does not follow this sequence pattern, amyloid-ß (16-22), readily coassembles into rippled ß-sheets. Equimolar mixtures of enantiomeric amyloid-ß (16-22) peptides assemble into supramolecular structures that exhibit distinct morphologies from those observed by self-assembly of the single enantiomer pleated ß-sheet fibrils. Formation of rippled ß-sheets composed of alternating l- and d-amyloid-ß (16-22) is confirmed by isotope-edited infrared spectroscopy and solid-state NMR spectroscopy. Sedimentation analysis reveals that rippled ß-sheet formation by l- and d-amyloid-ß (16-22) is energetically favorable relative to self-assembly into corresponding pleated ß-sheets. This work illustrates that coassembly of enantiomeric ß-sheet peptides into rippled ß-sheets is not limited to peptides with alternating hydrophobic/hydrophilic sequence patterns, but that a broader range of sequence space is available for the design and preparation of rippled ß-sheet materials.


Assuntos
Peptídeos beta-Amiloides/química , Sequência de Aminoácidos , Humanos , Espectroscopia de Ressonância Magnética , Modelos Moleculares , Estrutura Molecular , Conformação Proteica em Folha beta , Multimerização Proteica , Espectrofotometria Infravermelho
12.
Chemphyschem ; 20(13): 1680-1689, 2019 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-31087613

RESUMO

We employed deuterium solid-state NMR techniques under static conditions to discern the details of the µs-ms timescale motions in the flexible N-terminal subdomain of Aß1-40 amyloid fibrils, which spans residues 1-16. In particular, we utilized a rotating frame (R1ρ ) and the newly developed time domain quadrupolar Carr-Purcell-Meiboom-Gill (QCPMG) relaxation measurements at the selectively deuterated side chains of A2, H6, and G9. The two experiments are complementary in terms of probing somewhat different timescales of motions, governed by the tensor parameters and the sampling window of the magnetization decay curves. The results indicated two mobile "free" states of the N-terminal domain undergoing global diffusive motions, with isotropic diffusion coefficients of 0.7-1 ⋅ 108 and 0.3-3 ⋅ 106 ad2 s-1 . The free states are also involved in the conformational exchange with a single bound state, in which the diffusive motions are quenched, likely due to transient interactions with the structured hydrophobic core. The conformational exchange rate constants are 2-3 ⋅ 105  s-1 and 2-3 ⋅ 104  s-1 for the fast and slow diffusion free states, respectively.


Assuntos
Peptídeos beta-Amiloides/química , Amiloide/química , Fragmentos de Peptídeos/química , Deutério , Ressonância Magnética Nuclear Biomolecular , Conformação Proteica , Domínios Proteicos
13.
J Biol Chem ; 294(15): 5840-5853, 2019 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-30737281

RESUMO

Amyloid fibril deposits observed in Alzheimer's disease comprise amyloid-ß (Aß) protein possessing a structured hydrophobic core and a disordered N-terminal domain (residues 1-16). The internal flexibility of the disordered domain is likely essential for Aß aggregation. Here, we used 2H static solid-state NMR methods to probe the dynamics of selected side chains of the N-terminal domain of Aß1-40 fibrils. Line shape and relaxation data suggested a two-state model in which the domain's free state undergoes a diffusive motion that is quenched in the bound state, likely because of transient interactions with the structured C-terminal domain. At 37 °C, we observed freezing of the dynamics progressively along the Aß sequence, with the fraction of the bound state increasing and the rate of diffusion decreasing. We also found that without solvation, the diffusive motion is quenched. The solvent acted as a plasticizer reminiscent of its role in the onset of global dynamics in globular proteins. As the temperature was lowered, the fraction of the bound state exhibited sigmoidal behavior. The midpoint of the freezing curve coincided with the bulk solvent freezing for the N-terminal residues and increased further along the sequence. Using 2H R 1ρ measurements, we determined the conformational exchange rate constant between the free and bound states under physiological conditions. Zinc-induced aggregation leads to the enhancement of the dynamics, manifested by the faster conformational exchange, faster diffusion, and lower freezing-curve midpoints.


Assuntos
Peptídeos beta-Amiloides/química , Simulação de Dinâmica Molecular , Fragmentos de Peptídeos/química , Zinco/química , Humanos , Ressonância Magnética Nuclear Biomolecular , Domínios Proteicos
14.
Angew Chem Int Ed Engl ; 57(37): 11918-11923, 2018 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-30040187

RESUMO

Na2 FePO4 F is a promising cathode material for Na-ion batteries owing to its relatively high discharge voltage and excellent cycling performance. Now, the long- and short-range structural evolution of Na2 FePO4 F during cycling is studied by in situ high-energy X-ray diffraction (XRD), ex situ solid-state nuclear magnetic resonance (NMR), and first-principles DFT calculations. DFT calculations suggest that the intermediate phase, Na1.5 FePO4 F, adopts the space group of P21 /c, which is a subgroup (P21 /b11, No. 14) of Pbcn (No. 60), the space group of the starting phase, Na2 FePO4 F, and this space group provides a good fit to the experimental XRD and NMR results. The two crystallographically unique Na sites in the structure of Na2 FePO4 F behave differently during cycling, where the Na ions on the Na2 site are electrochemically active while those on the Na1 site are inert. This study determines the structural evolution and the electrochemical reaction mechanisms of Na2 FePO4 F in a Na-ion battery.

15.
J Magn Reson ; 294: 83-92, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30015126

RESUMO

Multiple pulse sequences are often used to manipulate spin Hamiltonians in solid-state nuclear magnetic resonance spectroscopy. In this paper, we analyze multiple pulse sequences using the well-known average Hamiltonian theory. We first expand the resulting average Hamiltonian into a reachable set of sub-Hamiltonians and then develop a general procedure using both flip-angle and phase of the applied pulses as control variables to select any of those sub-Hamiltonians. We use this method to analyze solid-echo based sequences and to design new proton-proton homonuclear decoupling sequences in static solids. It is found that this newly designed decoupling scheme, in the presence of finite pulse length, effectively suppresses the 1H-1H homonuclear dipolar interactions while establishes variable scaling factors on the heteronuclear dipolar interactions and chemical shift interactions, depending on the flip-angle of the applied pulses. When the pulse flip-angle is close to 54.7°, this sequence possesses a large scaling factor with relatively low average decoupling field. When the pulse flip-angle becomes ∼120°, the scaling factor is almost zero. A static 15N-acetyl-valine crystal sample has been used as an example to confirm and validate the performance of this new decoupling scheme.

16.
J Magn Reson ; 293: 34-40, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-29890484

RESUMO

A small flip-angle pulse direct polarization is the simplest method commonly used to quantify various compositions in many materials applications. This method sacrifices the sensitivity per scan in exchange for rapid repeating of data acquisition for signal accumulation. In addition, the resulting spectrum often encounters artifacts from background signals from probe components and/or from acoustic rings leading to a distorted baseline, especially in low-γ nuclei and wideline NMR. In this work, a multi-acquisition scheme is proposed to boost the sensitivity per scan and at the same time effectively suppress these artifacts. Here, an adiabatic inversion pulse is first applied in order to bring the magnetization from the +z to -z axis and then a small flip-angle pulse excitation is used before the data acquisition. Right after the first acquisition, the adiabatic inversion pulse is applied again to flip the magnetization back to the +z axis. The second data acquisition takes place after another small flip-angle pulse excitation. The difference between the two consecutive acquisitions cancels out any artifacts, while the wanted signals are accumulated. This acquisition process can be repeated many times before going into next scan. Therefore, by acquiring the signals multiple times in a single scan the sensitivity is improved. A mixture sample of flufenamic acid and 3,5-difluorobenzoic acid and a titanium silicate sample have been used to demonstrate the advantages of this newly proposed method.

17.
J Am Chem Soc ; 140(25): 7885-7895, 2018 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-29799200

RESUMO

Aquaporin Z (AqpZ) is an integral membrane protein that facilitates transport of water across Escherichia coli cells with a high rate. Previously, R189, a highly conserved residue of the selective filter of AqpZ, was proposed as a gate within the water channel on the basis of the observation of both open and closed conformations of its side chain in different monomers of an X-ray structure, and the observation of rapid switches between the two conformations in molecular dynamic simulations. However, the gating mechanism of the R189 side chain remains controversial since it is unclear whether the different conformations observed in the X-ray structure is due to different functional states or is a result of perturbation of non-native detergent environments. Herein, in native-like synthetic bilayers and native E. coli membranes, a number of solid-state NMR techniques are employed to examine gating mechanism of the R189 side chain of AqpZ. One R189 side-chain conformation is highly evident since only a set of peaks corresponding to the R189 side chain is observed in 2D 15N-13C spectra. The immobility of the R189 side chain is detected by 1H-15N dipolar lineshapes, excluding the possibility of the rapid switches between the two side-chain conformations. High-resolution monomeric structure of AqpZ, determined by CS-Rosetta calculations using experimentally measured distance restraints related to the R189 side chain, reveals that this side chain is in an open conformation, which is further verified by its water accessibility. All the solid-state NMR experimental results, combining with water permeability essay, suggest a permanently open conformation of the R189 side chain in the synthetic bilayer and native membranes. This study provides new structural insights into the gating mechanism of aquaporins and highlights the significance of lipid bilayer environments in elucidating the molecular mechanism of membrane proteins.

18.
J Magn Reson ; 287: 91-98, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29324246

RESUMO

The feasibility of using the spin-echo based diagonal peak suppression method in solid-state MAS NMR homonuclear chemical shift correlation experiments is demonstrated. A complete phase cycling is designed in such a way that in the indirect dimension only the spin diffused signals are evolved, while all signals not involved in polarization transfer are refocused for cancellation. A data processing procedure is further introduced to reconstruct this acquired spectrum into a conventional two-dimensional homonuclear chemical shift correlation spectrum. A uniformly 13C, 15N labeled Fmoc-valine sample and the transmembrane domain of a human protein, LR11 (sorLA), in native Escherichia coli membranes have been used to illustrate the capability of the proposed method in comparison with standard 13C-13C chemical shift correlation experiments.

19.
ACS Appl Mater Interfaces ; 9(50): 43632-43639, 2017 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-29164850

RESUMO

The development of highly reversible multielectron reaction per redox center in sodium super ionic conductor-structured cathode materials is desired to improve the energy density of sodium-ion batteries. Here, we investigated more than one-electron storage of Na in Na3VCr(PO4)3. Combining a series of advanced characterization techniques such as ex situ 51V solid-state nuclear magnetic resonance, X-ray absorption near-edge structure, and in situ X-ray diffraction, we reveal that V3+/V4+ and V4+/V5+ redox couples in the materials can be accessed, leading to a 1.5-electron reaction. It is also found that a light change on the local electronic and structural states or phase change could be observed after the first cycle, resulting in the fast capacity fade at room temperature. We also showed that the irreversibility of the phase changes could be largely suppressed at low temperature, thus leading to a much improved electrochemical performance.

20.
FEBS J ; 284(21): 3662-3683, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28892294

RESUMO

Host-defense peptides (HDPs) feature evolution-tested potency against life-threatening pathogens. While piscidin 1 (p1) and piscidin 3 (p3) are homologous and potent fish HDPs, only p1 is strongly membranolytic. Here, we hypothesize that another mechanism imparts p3 strong potency. We demonstrate that the N-termini of both peptides coordinate Cu2+ and p3-Cu cleaves isolated DNA at a rate on par with free Cu2+ but significantly faster than p1-Cu. On planktonic bacteria, p1 is more antimicrobial but only p3 features copper-dependent DNA cleavage. On biofilms and persister cells, p3-Cu is more active than p1-Cu, commensurate with stronger peptide-induced DNA damage. Molecular dynamics and NMR show that more DNA-peptide interactions exist with p3 than p1, and the peptides adopt conformations simultaneously poised for metal- and DNA-binding. These results generate several important conclusions. First, homologous HDPs cannot be assumed to have identical mechanisms since p1 and p3 eradicate bacteria through distinct relative contributions of membrane and DNA-disruptive effects. Second, the nuclease and membrane activities of p1 and p3 show that naturally occurring HDPs can inflict not only physicochemical but also covalent damage. Third, strong nuclease activity is essential for biofilm and persister cell eradication, as shown by p3, the homolog more specific toward bacteria and more expressed in vascularized tissues. Fourth, p3 combines several physicochemical properties (e.g., Amino Terminal Copper and Nickel binding motif; numerous arginines; moderate hydrophobicity) that confer low membranolytic effects, robust copper-scavenging capability, strong interactions with DNA, and fast nuclease activity. This new knowledge could help design novel therapeutics active against hard-to-treat persister cells and biofilms.


Assuntos
Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/metabolismo , Biofilmes/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Proteínas de Peixes/metabolismo , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Animais , Antibacterianos/isolamento & purificação , Antibacterianos/metabolismo , Peptídeos Catiônicos Antimicrobianos/isolamento & purificação , Clivagem do DNA/efeitos dos fármacos , Escherichia coli/citologia , Escherichia coli/crescimento & desenvolvimento , Proteínas de Peixes/isolamento & purificação , Peixes , Testes de Sensibilidade Microbiana , Simulação de Dinâmica Molecular , Pseudomonas aeruginosa/citologia , Pseudomonas aeruginosa/crescimento & desenvolvimento , Staphylococcus aureus/citologia , Staphylococcus aureus/crescimento & desenvolvimento
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