The Mechanism of Na+/K+ Selectivity in Mammalian Voltage-Gated Sodium Channels Based on Molecular Dynamics Simulation

AbstractVoltage-gated sodium (Nav) channels and their Na+/K+ selectivity are of great importance in the mammalian neuronal signaling. According to mutational analysis, the Na+/K+ selectivity in mammalian Nav channels is mainly determined by the Lys and Asp/Glu residues located at the constriction site within the selectivity filter. Despite successful molecular dynamics simulations conducted on the prokaryotic Nav channels, the lack of Lys at the constriction site of prokaryotic Nav channels limits how much can be learned about the Na+/K+ selectivity in mammalian Nav channels. In this work, we modeled the mammalian Nav channel by mutating the key residues at the constriction site in a prokaryotic Nav channel (NavRh) to its mammalian counterpart. By simulating the mutant structure, we found that the Na+ preference in mammalian Nav channels is collaboratively achieved by the deselection from Lys and the selection from Asp/Glu within the constriction site

Mechanical behavior of HTS coils in high field magnets based on the electromechanical coupling

International audienceWith the increase of both current-carrying capability and mechanical performance, 2G HTS tape is gradually becoming the dominant materials in the high field magnet. HTS coil co-wound by the REBCO coated conductor and insulated material is the insert coils, while the LTS coils usually provide a high background field. Both LTS coils and HTS coils together contribute to a high central magnetic field to meet the design requirements. However, due to the shielding current effect in coated conductor, the central field contributed by the HTS coils deviates from the design field. Moreover, HTS coils in normal operation would withstand the large electromagnetic force. Under the combined effect of electromagnetic force and thermal strain, the coated conductor may experience a large deformation. Investigations of the electro-mechanical characteristics in REBCO coated conductor is vital as the large strain in superconducting layer would cause the degradation of critical current. Thus, 2D electro- mechanical coupling numerical model is adopted, in which the Ic degradation caused by the strain is taken into account. The profiles of magnetic field and current density in HTS coils are presented for the cases with and without the electro- mechanical coupling effect. Then, the effect of shielding current on the distributions of magnetic field in HTS coils is discussed. The profiles of stress and strain of HTS coils in high field are calculated. The maximum stresses in the coil for different cases are also analyz

Lysine and the Na+/K+ Selectivity in Mammalian Voltage-Gated Sodium Channels.

Voltage-gated sodium (Nav) channels are critical in the generation and transmission of neuronal signals in mammals. The crystal structures of several prokaryotic Nav channels determined in recent years inspire the mechanistic studies on their selection upon the permeable cations (especially between Na+ and K+ ions), a property that is proposed to be mainly determined by residues in the selectivity filter. However, the mechanism of cation selection in mammalian Nav channels lacks direct explanation at atomic level due to the difference in amino acid sequences between mammalian and prokaryotic Nav homologues, especially at the constriction site where the DEKA motif has been identified to determine the Na+/K+ selectivity in mammalian Nav channels but is completely absent in the prokaryotic counterparts. Among the DEKA residues, Lys is of the most importance since its mutation to Arg abolishes the Na+/K+ selectivity. In this work, we modeled the pore domain of mammalian Nav channels by mutating the four residues at the constriction site of a prokaryotic Nav channel (NavRh) to DEKA, and then mechanistically investigated the contribution of Lys in cation selection using molecular dynamics simulations. The DERA mutant was generated as a comparison to understand the loss of ion selectivity caused by the K-to-R mutation. Simulations and free energy calculations on the mutants indicate that Lys facilitates Na+/K+ selection by electrostatically repelling the cation to a highly Na+-selective location sandwiched by the carboxylate groups of Asp and Glu at the constriction site. In contrast, the electrostatic repulsion is substantially weakened when Lys is mutated to Arg, because of two intrinsic properties of the Arg side chain: the planar geometric design and the sparse charge distribution of the guanidine group

Mechanical behavior of HTS coils in high field magnets based on the electromechanical coupling

International audienceWith the increase of both current-carrying capability and mechanical performance, 2G HTS tape is gradually becoming the dominant materials in the high field magnet. HTS coil co-wound by the REBCO coated conductor and insulated material is the insert coils, while the LTS coils usually provide a high background field. Both LTS coils and HTS coils together contribute to a high central magnetic field to meet the design requirements. However, due to the shielding current effect in coated conductor, the central field contributed by the HTS coils deviates from the design field. Moreover, HTS coils in normal operation would withstand the large electromagnetic force. Under the combined effect of electromagnetic force and thermal strain, the coated conductor may experience a large deformation. Investigations of the electro-mechanical characteristics in REBCO coated conductor is vital as the large strain in superconducting layer would cause the degradation of critical current. Thus, 2D electro- mechanical coupling numerical model is adopted, in which the Ic degradation caused by the strain is taken into account. The profiles of magnetic field and current density in HTS coils are presented for the cases with and without the electro- mechanical coupling effect. Then, the effect of shielding current on the distributions of magnetic field in HTS coils is discussed. The profiles of stress and strain of HTS coils in high field are calculated. The maximum stresses in the coil for different cases are also analyz

Application of Quantum Dots for Photocatalytic Hydrogen Evolution Reaction

There is increased interest in the conversion of solar energy into green chemical energy because of the depletion of fossil fuels and their unpleasant environmental effect. Photocatalytic hydrogen generation from water involves the direct conversion of solar energy into H2 fuels, which exhibits significant advantages and immense promise. Nevertheless, photocatalytic efficiency is considerably lower than the standard range of industrial applications. Low light absorption efficiency, the rapid recombination of photogenerated electrons and holes, slow surface redox reaction kinetics and low photostability are well known to be key factors negatively affecting photocatalytic hydrogen production. Therefore, to construct highly efficient and stable photocatalysts is important and necessary for the development of photocatalytic hydrogen generation technology. In this review, quantum dots (QDs)-based photocatalysts have emerged with representative achievements. Due to their excellent light-harvesting ability, low recombination efficiency of photogenerated electrons and holes, and abundant surface active sites, QDs have attracted remarkable interest as photocatalysts and/or cocatalyst for developing highly efficient photocatalysts. In this review, the application of QDs for photocatalytic H2 production is emphatically introduced. First, the special photophysical properties of QDs are briefly described. Then, recent progress into the research on QDs in photocatalytic H2 production is introduced, in three types: semiconductor QDs (e.g., CdS, CdMnS, and InP QDs), metal QDs (e.g., Au, Pt and Ag QDs), and MXene QDs and carbon QDs (CDQs). Finally, the challenges and prospects of photocatalytic H2 evolution with QDs in the future are discussed

New Insights into Xanthophylls and Lipidomic Profile Changes Induced by Glucose Supplementation in the Marine Diatom Nitzschia laevis

Nitzschia laevis is a candidate microorganism for bioactive compounds (fucoxanthin and eicosapentaenoic acid (EPA)) production. In this study, the impacts of glucose-induced trophic transition on biomass, photosynthesis, pigments, and lipid profiles were examined. The specific growth rate was increased under glucose addition, achieved at 0.47 day−1 (0.26 ± 0.01 day−1 for the group without glucose in medium). However, the photosynthetic parameters and pigments including chlorophylls, fucoxanthin, and diatoxanthin were reduced. The net yield of EPA doubled under glucose addition, reaching 20.36 ± 1.22 mg/L in 4 days. In addition, the alteration in detailed lipid molecular species was demonstrated with a focus on EPA-enriched lipids. The effects of 2-deoxyglucose (2DG) indicated that glucose phosphorylation was involved in glucose-induced regulation. These findings provide novel data for guiding the application of this diatom strain in the functional food industries

Diagram of the model to explain the difference in ion selectivity between the DEKA and DERA mutants.

<p>Na⁺ and K⁺ ions are represented by yellow and orange spheres respectively. <b>(a)</b> In the DEKA mutant, Lys180 side chain tends to protrude into the center of the SF, repelling the cation to bind at the Na⁺-preferred sub-location sandwiched by at least three carboxylate oxygen atoms of Asp180 and Glu180. <b>(b)</b> In the DERA mutant, because of the stable bifurcate interactions with Glu183 residues (in chain A and D), Arg180 side chain tends to line along the side wall of the SF pore. This conformational difference as well as the lower charge density on the guanidine group jointly weaken the electrostatic repulsion and allow the cation to sample the less Na⁺-selective or even K⁺-preferred sub-locations coordinated by no more than two carboxylate oxygen atoms of Asp180 and Glu180.</p

Ion binding patterns in the SF of the DEKA (a, b) and DERA (c, d) mutants of Na_vRh for Na⁺ (a, c) and K⁺ (b, d) ions in the a-system (IDs 13–16 in Table B in S1 File).

<p>For each map, the upper panel shows a representative structure obtained from the equilibrium simulation. The side chains of residues 180 are shown in the licorice representation for clarity. The SF is shown in the cartoon representation and colored in cyan. Na⁺ and K⁺ ions are represented as yellow and orange spheres respectively. The lower panel exhibits the 2D free energy profile (in the unit of kcal/mol) estimated from the probability density map of cations in SF that is counted from the corresponding 200 ns equilibrium simulation. The vertical axis is the relative distance of the cation to the geometric center of the SF along the z-axis, with labels denoting the binding sites (Ion_EX, Site_HFS, Site_CEN and Site_IN) proposed from the static crystal structure of Na_vAb. Positions of Site_OC are labeled by black arrows. The horizontal axis is the distance between cation and the geometric center of the SF projected in the xy-plane.</p

The structural representation and sequence alignment for the SFs of Na_v channels.

<p>In the structural representation (upper panel), the Na_vRh crystal structure is shown as an example, where only two of the four chains (A and C) are represented in cartoons for clarity. In the sequence alignment (lower panel), the sequences for two prokaryotic channels (Na_vRh and Na_vAb) as well as the four domains of one mammalian channel (human Na_v1.4) are compared side-by-side, with the P-loop of the SF region highlighted by a blue frame. Two rings of residues are highly conserved in mammalian Na_v channels: the inner ring (shaded in red) and the outer ring (shaded in blue). The positions of these two rings are labeled by dotted frames colored in red and blue respectively, in the structural representation (upper panel).</p

Two constraint-free short simulations on the DEKA mutant in NaCl.

<p>Na⁺ ions are represented as yellow spheres. <b>(a, b</b>) In the first simulation (ID 5 in Table B in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0162413#pone.0162413.s001" target="_blank">S1 File</a>), no Na⁺ ions (violet dots) can pass Lys180 side chain (blue line) to reach the interior Site_INT (<b>a</b>), and Lys180 side chain never falls within the interacting distances of any Glu183 residues (distances colored in black, red, green and blue for chain A, B, C and D respectively) (<b>b</b>). (<b>c-e</b>) In the second simulation (ID 6 in Table B in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0162413#pone.0162413.s001" target="_blank">S1 File</a>), the Na⁺ ion (violet dots) can cross Lys180 side chain (blue line) and arrive at Site_INT (<b>c</b>), and Lys180 side chain begins to interact with at least one of the Glu183 residues (distances colored in the same scheme) roughly at the same time. In the last 15 ns of this simulation, steady hydrogen bonds can form between Lys180 and Glu183 of chain A (<b>e</b>).</p