Browse
Submit Data
Databases
API
Help

Dataset Information

22 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Cation Selectivity in Biological Cation Channels Using Experimental Structural Information and Statistical Mechanical Simulation.

ABSTRACT: Cation selective channels constitute the gate for ion currents through the cell membrane. Here we present an improved statistical mechanical model based on atomistic structural information, cation hydration state and without tuned parameters that reproduces the selectivity of biological Na+ and Ca2+ ion channels. The importance of the inclusion of step-wise cation hydration in these results confirms the essential role partial dehydration plays in the bacterial Na+ channels. The model, proven reliable against experimental data, could be straightforwardly used for designing Na+ and Ca2+ selective nanopores.

SUBMITTER: Finnerty JJ

PROVIDER: S-EPMC4603898 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Cation Selectivity in Biological Cation Channels Using Experimental Structural Information and Statistical Mechanical Simulation.

Finnerty Justin John JJ Peyser Alexander A Carloni Paolo P

PloS one 20151013 10

Cation selective channels constitute the gate for ion currents through the cell membrane. Here we present an improved statistical mechanical model based on atomistic structural information, cation hydration state and without tuned parameters that reproduces the selectivity of biological Na+ and Ca2+ ion channels. The importance of the inclusion of step-wise cation hydration in these results confirms the essential role partial dehydration plays in the bacterial Na+ channels. The model, proven rel ...[more]

PMID: 26460827

Similar Datasets

Structural Plasticity of the Selectivity Filter in Cation Channels.

Project description:Ion channels allow for the passage of ions across biological membranes, which is essential for the functioning of a cell. In pore loop channels the selectivity filter (SF) is a conserved sequence that forms a constriction with multiple ion binding sites. It is becoming increasingly clear that there are several conformations and dynamic states of the SF in cation channels. Here we outline specific modes of structural plasticity observed in the SFs of various pore loop channels: disorder, asymmetry, and collapse. We summarize the multiple atomic structures with varying SF conformations as well as asymmetric and more dynamic states that were discovered recently using structural biology, spectroscopic, and computational methods. Overall, we discuss here that structural plasticity within the SF is a key molecular determinant of ion channel gating behavior.

| S-EPMC8689586 | biostudies-literature

Mechanical control of cation channels in the myogenic response.

Project description:Microcirculatory vessel response to changes in pressure, known as the myogenic response, is a key component of a tissue's ability to regulate blood flow. Experimental studies have not clearly elucidated the mechanical signal in the vessel wall governing steady-state reduction in vessel diameter upon an increase in intraluminal pressure. In this study, a multiscale computational model is constructed from established models of vessel wall mechanics, vascular smooth muscle (VSM) force generation, and VSM Ca(2+) handling and electrophysiology to compare the plausibility of vessel wall stress or strain as an effective mechanical signal controlling steady-state vascular contraction in the myogenic response. It is shown that, at the scale of a resistance vessel, wall stress, and not stretch (strain), is the likely physiological signal controlling the steady-state myogenic response. The model is then used to test nine candidate VSM stress-controlled channel variants by fitting two separate sets of steady-state myogenic response data. The channel variants include nonselective cation (NSC), supplementary Ca(2+) and Na(+), L-type Ca(2+), and large conductance Ca(2+)-activated K(+) channels. The nine variants are tested in turn, and model fits suggest that stress control of Ca(2+) or Na(+) influx through NSC, supplementary Ca(2+) or Na(+), or L-type Ca(2+) channels is sufficient to produce observed steady-state diameter changes with pressure. However, simulations of steady-state VSM membrane potential, cytosolic Ca(2+), and Na(+) with pressure show only that Na(+) influx through NSC channel also generates known trends with increasing pressure, indicating that stress-controlled Na(+) influx through NSC is sufficient to generate the myogenic response.

| S-EPMC3154678 | biostudies-literature

Quantum Interference and Selectivity through Biological Ion Channels.

Project description:The mechanism of selectivity in ion channels is still an open question in biology for more than half a century. Here, we suggest that quantum interference can be a solution to explain the selectivity mechanism in ion channels since interference happens between similar ions through the same size of ion channels. In this paper, we simulate two neighboring ion channels on a cell membrane with the famous double-slit experiment in physics to investigate whether there is any possibility of matter-wave interference of ions via movement through ion channels. Our obtained decoherence timescales indicate that the quantum states of ions can only survive for short times, i.e. ≈100 picoseconds in each channel and ≈17-53 picoseconds outside the channels, giving the result that the quantum interference of ions seems unlikely due to environmental decoherence. However, we discuss our results and raise few points, which increase the possibility of interference.

| S-EPMC5278555 | biostudies-literature

Structural basis for conductance through TRIC cation channels.

Project description:Mammalian TRICs function as K+-permeable cation channels that provide counter ions for Ca2+ handling in intracellular stores. Here we describe the structures of two prokaryotic homologues, archaeal SaTRIC and bacterial CpTRIC, showing that TRIC channels are symmetrical trimers with transmembrane pores through each protomer. Each pore holds a string of water molecules centred at kinked helices in two inverted-repeat triple-helix bundles (THBs). The pores are locked in a closed state by a hydrogen bond network at the C terminus of the THBs, which is lost when the pores assume an open conformation. The transition between the open and close states seems to be mediated by cation binding to conserved residues along the three-fold axis. Electrophysiology and mutagenesis studies show that prokaryotic TRICs have similar functional properties to those of mammalian TRICs and implicate the three-fold axis in the allosteric regulation of the channel.

| S-EPMC5477506 | biostudies-literature

Recovery of biological information under heterogeneous experimental conditions using subgroup standardization.

Project description:Recovery of biological information (i.e. Breast tumor versus non-tumor part of breast) from microarray data under heterogeneous experimental conditions (Buffer1 versus Buffer2) using subgroup standardization. Microarray is a useful tool for gene expression analysis and prediction. For a given disease, a microarray database may come from various sources with different experimental setups, collected over time. This heterogeneity provides unnecessary complication in data analysis and, even worse, given false classification in clustering. Therefore, it is practically important to provide a standard data treatment for microarray data from heterogeneous experimental conditions. In this work, “subgroup standardization” is proposed to compensate technical heterogeneities (e.g., buffers, time, machines etc.) in microarray experimental conditions. Provided with repetitive microarray experiments, over time and buffers, the results indicate that the proposed approach can extract correct biological information in the presence of technical irregularities. Hierarchical clustering is used to validate the effectiveness of the proposed approach. Keywords: disease state study

2007-10-20 | GSE9309 | GEO

Structural insight into Ca2+ specificity in tetrameric cation channels.

Project description:Apparent blockage of monovalent cation currents by the permeating blocker Ca(2+) is a physiologically essential phenomenon relevant to cyclic nucleotide-gated (CNG) channels. The recently determined crystal structure of a bacterial homolog of CNG channel pores, the NaK channel, revealed a Ca(2+) binding site at the extracellular entrance to the selectivity filter. This site is not formed by the side-chain carboxylate groups from the conserved acidic residue, Asp-66 in NaK, conventionally thought to directly chelate Ca(2+) in CNG channels, but rather by the backbone carbonyl groups of residue Gly-67. Here we present a detailed structural analysis of the NaK channel with a focus on Ca(2+) permeability and blockage. Our results confirm that the Asp-66 residue, although not involved in direct chelation of Ca(2+), plays an essential role in external Ca(2+) binding. Furthermore, we give evidence for the presence of a second Ca(2+) binding site within the NaK selectivity filter where monovalent cations also bind, providing a structural basis for Ca(2+) permeation through the NaK pore. Compared with other Ca(2+)-binding proteins, both sites in NaK present a novel mode of Ca(2+) chelation, using only backbone carbonyl oxygen atoms from residues in the selectivity filter. The external site is under indirect control by an acidic residue (Asp-66), making it Ca(2+)-specific. These findings give us a glimpse of the possible underlying mechanisms allowing Ca(2+) to act both as a permeating ion and blocker of CNG channels and raise the possibility of a similar chemistry governing Ca(2+) chelation in Ca(2+) channels.

| S-EPMC2000519 | biostudies-literature

Structural biology of cation channels important for lysosomal calcium release.

Project description:Calcium is one of the most important second messengers in cells. The uptake and release of calcium ions are conducted by channels and transporters. Inside a eukaryotic cell, calcium is stored in intracellular organelles including the endoplasmic reticulum (ER), mitochondrion, and lysosome. Lysosomes are acid membrane-bounded organelles serving as the crucial degradation and recycling center of the cell. Lysosomes involve in multiple important signaling events, including nutrient sensing, lipid metabolism, and trafficking. Hitherto, two lysosomal cation channel families have been suggested to function as calcium release channels, namely the Two-pore Channel (TPC) family, and the Transient Receptor Potential Channel Mucolipin (TRPML) family. Additionally, a few plasma membrane calcium channels have also been found in the lysosomal membrane under certain circumstances. In this review, we will discuss the structural mechanism of the cation channels that may be important for lysosomal calcium release, primarily focusing on the TPCs and TRPMLs.

| S-EPMC8752501 | biostudies-literature

Structural correlates of selectivity and inactivation in potassium channels.

Project description:Potassium channels are involved in a tremendously diverse range of physiological applications requiring distinctly different functional properties. Not surprisingly, the amino acid sequences for these proteins are diverse as well, except for the region that has been ordained the "selectivity filter". The goal of this review is to examine our current understanding of the role of the selectivity filter and regions adjacent to it in specifying selectivity as well as its role in gating/inactivation and possible mechanisms by which these processes are coupled. Our working hypothesis is that an amino acid network behind the filter modulates selectivity in channels with the same signature sequence while at the same time affecting channel inactivation properties. This article is part of a Special Issue entitled: Membrane protein structure and function.

| S-EPMC3253935 | biostudies-literature

Structural basis for ion selectivity in TMEM175 K+ channels.

Project description:The TMEM175 family constitutes recently discovered K+channels that are important for autophagosome turnover and lysosomal pH regulation and are associated with the early onset of Parkinson Disease. TMEM175 channels lack a P-loop selectivity filter, a hallmark of all known K+ channels, raising the question how selectivity is achieved. Here, we report the X-ray structure of a closed bacterial TMEM175 channel in complex with a nanobody fusion-protein disclosing bound K+ ions. Our analysis revealed that a highly conserved layer of threonine residues in the pore conveys a basal K+ selectivity. An additional layer comprising two serines in human TMEM175 increases selectivity further and renders this channel sensitive to 4-aminopyridine and Zn2+. Our findings suggest that large hydrophobic side chains occlude the pore, forming a physical gate, and that channel opening by iris-like motions simultaneously relocates the gate and exposes the otherwise concealed selectivity filter to the pore lumen.

| S-EPMC7176437 | biostudies-literature

Experimental and Statistical Study on Mechanical Characteristics of Geopolymer Concrete.

Project description:This paper studies the statistical correlation in mechanical characteristics of class F fly ash based geopolymer concrete (CFGPC). Experimentally measured values of the compressive strength, elastic modulus and indirect tensile strength of CFGPC specimens made from class F fly ash (CFA) were presented and analyzed. The results were compared with those of corresponding ordinary Portland cement concrete (OPCC) using statistical hypothesis tests. Results illustrated that when possessing similar compressive and tensile strength, the elastic modulus for CFGPC is significantly lower than that of OPCC. The corresponding expressions recommended by standards for the case of OPCC is proved to be inaccurate when applied in the case of CFGPC. Statistical regression was used to identify tendencies and correlations within the mechanical characteristics of CFGPC, as well as the empirical equations for predicting tensile strength and elastic modulus of CFGPC from its compressive strength values. In conclusion, CFGPC and OPCC has significant differences in terms of the correlations between mechanical properties. The empirical equations obtained in this study could provide relatively accurate predictions on the mechanical behavior of CFGPC.

| S-EPMC7178337 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data