Mechanism Of Ion Selectivity Research Articles

Charge govern ion-selective mechanism of YX2 desalination pore using high-throughput computations and machine learning

Energy-efficient and low-cost desalination of water continues to be a problem that society is facing. With the advances in nanotechnology, a variety of nanopore membranes have emerged for desalination. In particular, YX2 nanopores (YW, Mo, etc. and X = S, Se, Te, etc.) have been considered as promising membranes for water purification. In this work, we used a combination of high-throughput molecular dynamics simulations and machine learning to reveal the nanopore mass transfer mechanism and rationally design the YX2 nanopore. The pore size and the charge of the pore mouth were found to be the main factors affecting water permeation and salt rejection, as discovered through the machine learning study. The physical-chemical analysis provides us with a deep understanding of the charge-governed mechanism on the desalination performance of YX2 nanopores. It revealed that YX2 nanopores with a conical shape and minimized pore charges could be ideal candidates for excellent desalination performance. Based on this, we designed the YX2 pore with a specific charge distribution, which could achieve high water permeation with high salt rejection. Therefore, the combination of machine learning and high-throughput computation methods could aid in designing materials with excellent performance for desalination.

Structural insights into ion selectivity and transport mechanisms of Oryza sativa HKT2;1 and HKT2;2/1 transporters.

Plant high-affinity K+ transporters (HKTs) play a pivotal role in maintaining the balance of Na+ and K+ ions in plants, thereby influencing plant growth under K+-depleted conditions and enhancing tolerance to salinity stress. Here we report the cryo-electron microscopy structures of Oryza sativa HKT2;1 and HKT2;2/1 at overall resolutions of 2.5 Å and 2.3 Å, respectively. Both transporters adopt a dimeric assembly, with each protomer enclosing an ion permeation pathway. Comparison between the selectivity filters of the two transporters reveals the critical roles of Ser88/Gly88 and Val243/Gly243 in determining ion selectivity. A constriction site along the ion permeation pathway is identified, consisting of Glu114, Asn273, Pro392, Pro393, Arg525, Lys517 and the carboxy-terminal Trp530 from the neighbouring protomer. The linker between domains II and III adopts a stable loop structure oriented towards the constriction site, potentially participating in the gating process. Electrophysiological recordings, yeast complementation assays and molecular dynamics simulations corroborate the functional importance of these structural features. Our findings provide crucial insights into the ion selectivity and transport mechanisms of plant HKTs, offering valuable structural templates for developing new salinity-tolerant cultivars and strategies to increase crop yields.

The Molecular Mechanism of Ion Selectivity in Nanopores.

Ion channels exhibit strong selectivity for specific ions over others under electrochemical potentials, such as KcsA for K+ over Na+. Based on the thermodynamic analysis, this study is focused on exploring the mechanism of ion selectivity in nanopores. It is well known that ions must lose part of their hydration layer to enter the channel. Therefore, the ion selectivity of a channel is due to the rearrangement of water molecules when entering the nanopore, which may be related to the hydrophobic interactions between ions and channels. In our recent works on hydrophobic interactions, with reference to the critical radius of solute (Rc), it was divided into initial and hydrophobic solvation processes. Additionally, the different dissolved behaviors of solutes in water are expected in various processes, such as dispersed and accumulated distributions in water. Correspondingly, as the ion approaches the nanopore, there seems to exist the "repulsive" or "attractive" forces between them. In the initial process (<Rc), the energy barrier related to "repulsive" force may be expected as ions enter the channel. Regarding the ion selectivity of nanopores, this may be due to the energy barrier between the ion and channel, which is closely related to the ion size and pore radius. Additionally, these may be demonstrated by the calculated potential mean forces (PMFs) using molecular dynamics (MD) simulations.

Mechanism of lithium ion selectivity through membranes: a brief review

The ion transportation process through a membrane was divided into 3 sequential stages, where the ion selectivity could be determined by the ion charge, hydration energy, channel size and surface chemistry.

Separation of nutrients and acetate from sewage sludge fermentation liquid in flow-electrode capacitive deionization system: Competitive mechanisms of ions and influence of activated carbon

Effective separation of volatile fatty acids (VFAs), ammonia (NH4+-N) and reactive phosphorous (RP) generated from anaerobic fermentation liquid is critically important for efficient resource recovery. Flow-electrode capacitive deionization (FCDI) is proven to be capable of efficient removal of ions, environmentally friendly and cost-effective in operation. The performances of FCDI system in the separation of NH4+-N, RP, and acetate and mechanism of pHs and activated carbon on their performances were investigated. Results showed that a pH of 5.0 promoted the removal of NH4+-N (53.1 %) and RP (39.5 %), and 72.0 % of acetate was retained in the solution, which revealed that removal of NH4+-N and RP, and retention of acetate were evidently affected by speciation of ions. Furthermore, the recovery of NH4+-N and RP was undermined by the adsorption of ions on activated carbon. This study provides a novel insight of ion selective mechanism during the operation of the FCDI system.

A potential-driven NiO/NiCo LDH film electrode for highly efficient extraction of Br- via electrochemical coordination and anion exchange

A potential-driven nickel oxide/NiCo layered double hydroxide (NiO/NiCo LDH) composite film was deposited within the stainless steel wire mesh, showing excellent Br− extraction in an electrochemically switched ion exchange (ESIX) system. In this composite film, NiO with a high specific surface area and porous structure served as the lower layer to improve the electrical conductivity and ion storage capacity of the film, while NiCo LDH served as the main selective separation layer to selectively adsorb the target Br−. The film electrode extracted Br− up to 159.25 mg·g−1 and the separation factors of Br−/Cl−, Br−/NO3−, and Br−/I− were 2.04, 8.89, and 5.45, respectively. The film electrode showed excellent adsorption–desorption cyclability and electrochemical stability since the NiO increased the binding force and electrical conductivity between NiCo LDH and substrate, and its porous structure accommodated Br−. The highly efficient extraction of Br− in neutral solution was attributed to the electrochemical coordination and interlayer anion exchange sites of NiO/NiCo LDH. This study provided a deep understanding of the ion selective extraction mechanism of LDH-based materials by ESIX technology and the novel electrochemical reaction design of electrodes, which could be used in other fields such as supercapacitors, sensors, and batteries.

Ensemble machine learning reveals key structural and operational features governing ion selectivity of polyamide nanofiltration membranes

Diversified ion-selective separation applications have dramatically incentivized the exploitation and performance modulation of highly ion-selective nanofiltration (NF) membranes. However, the ion selectivity of NF membranes is synergistically governed by multi-scale factors of membrane structural parameters and operational parameters, with the intrinsic ion-selective mechanism still ambiguous. Herein, we proposed an ensemble machine learning (ML) method to decouple key factors affecting the ionic selectivity of polyamide NF membranes. Membrane structural parameters and operational parameters were typically extracted as input variables and linked to mono−/divalent ion selectivity by model training based on Random Forest and XGBoost algorithms. The feature importance assessment indicated the critical role of membrane structure parameters on ion selectivity, wherein pore radius dominated the mono−/divalent anionic selectivity while zeta potential for mono−/divalent cationic selectivity. Partial dependence analyses further depicted intensive insights regarding the influence of membrane structural parameters on ion selectivity. Moreover, stochastic dataset splitting measurements demonstrated the accurate predictive capability of the model simultaneously possessing excellent stability and reliability. We anticipated that the implementation of ensemble ML in explicating the intricate ion-selective mechanism created platforms for understanding the structure-membrane performance correlation and orientally manufacturing highly ion-selective NF membranes.

Re-assessing the role of the helix bundle crossing in NaK.

Potassium channels play the main role in shaping action potentials across all living organisms. This function is owed to their ability to open and close in response to stimuli, and thus conduct ions in a selective and regulated fashion. Small prokaryotic potassium channels, such as KcsA, have become model systems for investigations of structure, dynamics and function. These channels are amenable to studies by various biophysical techniques and have been used to obtain insight into the molecular mechanisms of ion channel gating and selectivity. In the case of KcsA, the inner gate is allosterically coupled with the selectivity filter, and several ion conduction mechanisms across the selectivity filter have been proposed. To understand how general these gating and selectivity mechanisms are, we have used solution NMR spectroscopy and solid-supported membrane electrophysiology (SSME) to study another small prokaryotic channel NaK. While NaK maintains a very high degree of structural conservation to potassium channel pores, the conformation of the NaK selectivity filter is different. We show that while NaK still displays allosteric coupling between the selectivity filter and the helix bundle crossing, akin to what was observed for KcsA, the helix bundle crossing remains fully open in both conductive and non-conductive channels. In addition, using SSME we find that ion conduction by NaK shows K+ selectivity in the absence of an electric gradient. These observations contrast with the most recent models proposed by NMR and MD simulations on KcsA and other channels.

Structural and functional consequences of the H180A mutation of the light-driven sodium pump KR2

Krokinobacter eikastus rhodopsin 2 (KR2) is a light-driven pentameric sodium pump. Its ability to translocate cations other than protons and to create an electrochemical potential makes it an attractive optogenetic tool. Tailoring its ion-pumping characteristics by mutations is therefore of great interest. In addition, understanding the functional and structural consequences of certain mutations helps to derive a functional mechanism of ion selectivity and transfer of KR2. Based on solid-state NMR spectroscopy, we report an extensive chemical shift resonance assignment of KR2 within lipid bilayers. This data set was then used to probe site-resolved allosteric effects of sodium binding, which revealed multiple responsive sites including the Schiff base nitrogen and the NDQ motif. Based on this data set, the consequences of the H180A mutation are probed. The mutant is silenced in the presence of sodium while in its absence proton pumping is observed. Our data reveal specific long-range effects along the sodium transfer pathway. These experiments are complemented by time-resolved optical spectroscopy. Our data suggest a model in which sodium uptake by the mutant can still take place, while sodium release and backflow control are disturbed.

Mechanisms of ion selectivity and throughput in the mitochondrial calcium uniporter.

The mitochondrial calcium uniporter, which regulates aerobic metabolism by catalyzing mitochondrial Ca2+ influx, is arguably the most selective ion channel known. The mechanisms for this exquisite Ca2+ selectivity have not been defined. Here, using a reconstituted system, we study the electrical properties of the channel's minimal Ca2+-conducting complex, MCU-EMRE, from Tribolium castaneum to probe ion selectivity mechanisms. The wild-type TcMCU-EMRE complex recapitulates hallmark electrophysiological properties of endogenous Uniporter channels. Through interrogation of pore-lining mutants, we find that a ring of glutamate residues, the "E-locus," serves as the channel's selectivity filter. Unexpectedly, a nearby "D-locus" at the mouth of the pore has diminutive influence on selectivity. Anomalous mole fraction effects indicate that multiple Ca2+ ions are accommodated within the E-locus. By facilitating ion-ion interactions, the E-locus engenders both exquisite Ca2+ selectivity and high ion throughput. Direct comparison with structural information yields the basis for selective Ca2+ conduction by the channel.

Ion selectivity mechanism of the MgtE channel for Mg2+ over Ca2.

MgtE is a Mg2+-selective ion channel whose orthologs are widely distributed from prokaryotes to eukaryotes, including humans, and are important participants in the maintenance of cellular Mg2+ homeostasis. The previous high-resolution structure determination of the MgtE transmembrane (TM) domain in complex with Mg2+ ions revealed a recognition mechanism of MgtE for Mg2+ ions. In contrast, the previous Ca2+-bound structure of the MgtE TM domain was determined only at moderate resolution (3.2Å resolution), which was insufficient to visualize the water molecules coordinated to Ca2+ ions. Here, we showed that the metal-binding site of the MgtE TM domain binds to Mg2+ ∼500-fold more strongly than to Ca2+. We then determined the crystal structure of the MgtE TM domain in complex with Ca2+ ions at a higher resolution (2.5Å resolution), revealing hexahydrated Ca2+. These results provide mechanistic insights into the ion selectivity of MgtE for Mg2+ over Ca2+.

Multiple Li+ extraction mechanisms of sulfate saline by graphene nanopores: Effects of ion association under electric fields

In this work, the extraction of Li+ from sulfate solution by functionalized nanopores under various electric fields was investigated by molecular dynamics simulation. It was found that the dynamics of ion association and dissociation near nanopores play an important role in regulating the ion selectivity mechanism. When a strong electric field is applied (1.4 V nm−1), the ion transport can be affected by ion association enhanced near nanopore and the following dissociation near nanopore. Mg2+ is affected more apparently by ion association characteristics near nanopores than Li+, and thus rendering Li+ selectivity. Good separation of Mg2+ and Li+ can also be achieved by large nanopores of 3.5 nm, which is beneficial for the reverse migration of Mg2+ included in negatively charged structures. Alternatively, the strong association of Mg2+ with the COO− groups of nanopores may also be an important factor of Li+ selectivity under a relatively weaker electric field (0.6 V nm−1) for smaller nanopores (∼1.2 nm) and a dilute solution. Our results provide inspiration for the practical separation and purification of Li+ from sulfate-type saline.

Mechanism of high affinity potassium transporter (HKT) towards improved crop productivity in saline agricultural lands.

Glycophytic plants are susceptible to salinity and their growth is hampered in more than 40mM of salt. Salinity not only affects crop yield but also limits available land for farming by decreasing its fertility. Presence of distinct traits in response to environmental conditions might result in evolutionary adaptations. A better understanding of salinity tolerance through a comprehensive study of how Na+ is transported will help in the development of plants with improved salinity tolerance and might lead to increased yield of crops growing in strenuous environment. Ion transporters play pivotal role in salt homeostasis and maintain low cytotoxic effect in the cell. High-affinity potassium transporters are the critical class of integral membrane proteins found in plants. It mainly functions to remove excess Na+ from the transpiration stream to prevent sodium toxicity in the salt-sensitive shoot and leaf tissues. However, there are large number of HKT proteins expressed in plants, and it is possible that these members perform in a wide range of functions. Understanding their mechanism and functions will aid in further manipulation and genetic transformation of different crops. This review focuses on current knowledge of ion selectivity and molecular mechanisms controlling HKT gene expression. The current review highlights the mechanism of different HKT transporters from different plant sources and how this knowledge could prove as a valuable tool to improve crop productivity.

Machine learning reveals key ion selectivity mechanisms in polymeric membranes with subnanometer pores.

Designing single-species selective membranes for high-precision separations requires a fundamental understanding of the molecular interactions governing solute transport. Here, we comprehensively assess molecular-level features that influence the separation of 18 different anions by nanoporous cellulose acetate membranes. Our analysis identifies the limitations of bulk solvation characteristics to explain ion transport, highlighted by the poor correlation between hydration energy and the measured permselectivity (R2 = 0.37). Entropy-enthalpy compensation, spanning 40 kilojoules per mole, leads to a free-energy barrier (∆G‡) variation of only ~8 kilojoules per mole across all anions. We apply machine learning to elucidate descriptors for energetic barriers from a set of 126 collected features. Notably, electrostatic features account for 75% of the overall features used to describe ∆G‡, despite the relatively uncharged state of cellulose acetate. Our work presents an approach for studying ion transport across nanoporous membranes that could enable the design of ion-selective membranes.

Effect of Lysine and Histidine Residues Modification on the Voltage Gating of the Mitochondrial Porin

Mitochondrial porin is a complex channel with many diverse functional properties. Therefore, along with measuring single-channel conductance and selectivity, monitoring VDAC&#39;s voltage gating has become the gold standard for assessing mitochondrial porin function.&nbsp; To understand the mechanisms of gating and ion selectivity, the detergent-solubilized porin was incubated with different concentrations of diethylpyrocarbonate (DEPC). The extent of the reaction of DEPC with histidine residues

Ion Selectivity in the ENaC/DEG Family: A Systematic Review with Supporting Analysis.

The Epithelial Sodium Channel/Degenerin (ENaC/DEG) family is a superfamily of sodium-selective channels that play diverse and important physiological roles in a wide variety of animal species. Despite their differences, they share a high homology in the pore region in which the ion discrimination takes place. Although ion selectivity has been studied for decades, the mechanisms underlying this selectivity for trimeric channels, and particularly for the ENaC/DEG family, are still poorly understood. This systematic review follows PRISMA guidelines and aims to determine the main components that govern ion selectivity in the ENaC/DEG family. In total, 27 papers from three online databases were included according to specific exclusion and inclusion criteria. It was found that the G/SxS selectivity filter (glycine/serine, non-conserved residue, serine) and other well conserved residues play a crucial role in ion selectivity. Depending on the ion type, residues with different properties are involved in ion permeability. For lithium against sodium, aromatic residues upstream of the selectivity filter seem to be important, whereas for sodium against potassium, negatively charged residues downstream of the selectivity filter seem to be important. This review provides new perspectives for further studies to unravel the mechanisms of ion selectivity.

The Integrative Approach to Study of the Structure and Functions of Cardiac Voltage-Dependent Ion Channels

Membrane proteins, including ion channels, became the focus of structural proteomics midway through the 20th century. Methods for studying ion channels are diverse and include structural (X-ray crystallography, cryoelectron microscopy, currently X-ray free electron lasers) and functional (e.g., patch clamp) approaches. This review highlights the evolution of approaches to study of the structure of cardiac ion channels, provides an overview of new techniques of structural biology concerning ion channels, including the use of lipo- and nanodiscs, and discusses the contribution of electrophysiological studies and molecular dynamics to obtain a complete picture of the structure and functioning of cardiac ion channels. Electrophysiological studies have become a powerful tool for deciphering the mechanisms of ion conductivity and selectivity, gating and regulation, as well as testing molecules of pharmacological interest. Obtaining the atomic structure of ion channels became possible by the active development of X-ray crystallography and cryoelectron micro-scopy, and, recently, with the use of XFEL.

Ion Selectivity and Permeation Mechanism in a Cyclodextrin-Based Channel.

Synthetic ion channels are a promising technology in the medical and materials sciences because of their ability to conduct ions. Channels based on cyclodextrin, a cyclic oligomer of glucose, are of particular interest because of their nontoxicity and biocompatibility. Using molecular dynamics-based free energy calculations, this study identifies cyclodextrin channel types that are best suited to serve as synthetic ion channels. Free energy profiles show that the connectivity in the channel determines whether the channel is cation-selective or anion-selective. Furthermore, the energy barrier for ion transport is governed by the number of glucose molecules making up the cyclodextrin units of the channel. A detailed mechanism is proposed for ion transport through these channels. Findings from this study will aid in designing cyclodextrin-based channels that could be either cation-selective or anion-selective, by modifying the linkages of the channel or the number of glucose molecules in the cyclodextrin rings.

Molecular mechanisms of ion conduction and ion selectivity in TMEM16 lipid scramblases

TMEM16 lipid scramblases transport lipids and also operate as ion channels with highly variable ion selectivities and various physiological functions. However, their molecular mechanisms of ion conduction and selectivity remain largely unknown. Using computational electrophysiology simulations at atomistic resolution, we identified the main ion-conductive state of TMEM16 lipid scramblases, in which an ion permeation pathway is lined by lipid headgroups that directly interact with permeating ions in a voltage polarity-dependent manner. We found that lipid headgroups modulate the ion-permeability state and regulate ion selectivity to varying degrees in different scramblase isoforms, depending on the amino-acid composition of the pores. Our work has defined the structural basis of ion conduction and selectivity in TMEM16 lipid scramblases and uncovered the mechanisms responsible for the direct effects of membrane lipids on the conduction properties of ion channels.

Fabrication of subnanochannels by metal–organic frameworks

Biological ion channels have prominent rectification and ion selectivity. Recent work published in <i>Nature Materials</i> by Huanting Wang and colleagues discloses that subnanochannels constructed by metal–organic frameworks (MOFSNC) can achieve monovalent metal ion selectivity and permeability with ultrahigh and pH-tunable features. The mechanism of ultra-high ion selectivity may be that the interaction between ions and carboxyl groups substantially reduces the energy barrier of monovalent cations passing through MOFSNC.