Engineering Papers⌕ Search

SEARCH · Engineering Papers

Results for “proton channel”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2020

Dimer interaction in the Hv1 proton channel

The voltage-gated proton channel Hv1 is a member of the voltage-gated ion channel superfamily, which stands out in design: It is a dimer of two voltage-sensing domains (VSDs), each containing a pore pathway, a voltage sensor (S4), and a gate (S1) and forming its own ion channel. Opening of the two channels in the dimer is cooperative. Part of the cooperativity is due to association between coiled-coil domains that extend intracellularly from the S4s. Interactions between the transmembrane portions of the subunits may also contribute, but the nature of transmembrane packing is unclear. Using functional analysis of a mutagenesis scan, biochemistry, and modeling, we find that the subunits form a dimer interface along the entire length of S1, and also have intersubunit contacts between S1 and S4. These interactions exert a strong effect on gating, in particular on the stability of the open state. Our results suggest that gating in Hv1 is tuned by extensive VSD–VSD interactions between the gates and voltage sensors of the dimeric channel.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS2002

The M2 Proton Channel of Influenza Virus: How Does It Work?

The transport of protons across membranes is an essential process for both bioenergetics of modem cells and the origins of cellular life. All living systems make use of proton gradients across cell walls to convert environmental energy into a high-energy chemical compound, adenosine triphosphate (ATR), synthesized from adenosine diphosphate. ATR, in turn, is used as a source of energy to drive many cellular reactions. The ubiquity of this process in biology suggests that even the earliest cellular systems were relying on proton gradient for harvesting environmental energy needed to support their survival and growth. In contemporary cells, proton transfer is assisted by large, complex proteins embedded in membranes. The issue addressed in this study was: how the same process can be accomplished with the aid of similar, but much simpler molecules that could have existed in the protobiological milieu? The model system used in the study contained a bilayer membrane made of phospholipid, dimyristoylphosphatidylcholine (DMPC), which is a good model of the biological membranes focusing cellular boundaries. Both sides of the bilayer were surrounded by water which simulated the environment inside and outside the cell. Embedded in the membrane was a fragment of the Influenza-A M2 protein and enough sodium counterions to maintain system neutrality. This protein has been shown to exhibit remarkably high rates of proton transport and, therefore, is an excellent model to study the formation of proton gradients across membranes. The Influenza M2 protein is 97 amino acids in length, but a fragment 25 amino acids long, which contains a transmembrane domain of 19 amino acids flanked by 3 amino acids on each side, is sufficient to transport protons. Four identical protein fragments, each folded into a helix, aggregate to form small channels spanning the membrane. Protons are conducted through a narrow pore in the middle of the channel in response to applied voltage. This channel is large enough to contain water molecules, and is normally filled with water. In analogy to the mechanism of proton transfer in some other channels, it has been postulated that protons are translocated along the network of water molecules filling the pore of the channel. This mechanism, however, must involve an additional, important step because the channel contains four histidine amino acid residues, one from each of the helices, which are sufficiently large to occlude the pore and interrupt the water network. The histidine residues ensure channel selectivity by blocking transport of small such as sodium or potassium. They have been also implicated in gating protons due to the ability of each histidine to become positively charged by accepting an additional proton. Two mechanisms of gating have been proposed. In one mechanism, all four histidines acquire an additional proton and, due to repulsion between their positive charges, move away from one another, thus opening the channel. The alternative mechanism relies of the ability of protons to move between different atoms in a molecule (tautomerization). Thus, a proton is captured on one side of the gate while another proton is released from the opposite side, and the molecule returns to the initial state through tautomerization. The simulations were designed to test these two mechanisms. Large-scale, atomic-level molecular dynamics simulations of the channel, in which the histidine residues were in different protonation states revealed that all intermediate states of the system involved in the tautomerization mechanism are structurally stable and the arrangement of water molecules in the channel is conducive to the proton transport. In contrast, in the four-protonated state, postulated to exist in the gate-opening mechanism, the electrostatic repulsion between the histidine residues appears to be so large that the channel looses its structural integrity and one helix moves away from the remaining three. This result indicates that such a mechanism of proton transport is unlikely. The simulations revealed that translocation along a network of water molecules in the channel and tautomerization of the histidine residues in the M2 proteins in the most likely mechanism of proton transport. The results not only explain how a remarkably simple protein system can efficiently aid in the formation of proton gradients across cell walls, but also suggest how this system can be genetically re-engineered to become a directional, reversible proton pump. Such a pump can provide energy to laboratory-built models of simple cellular systems. If they were successfully constructed it would greatly advance our understanding of the beginnings of life and find important applications in medicine and pharmacology.

Pohorille, Andrew↗
DOE OSTI2021

Structural dynamics in the water and proton channels of photosystem II during the S2 to S3 transition

Abstract Light-driven oxidation of water to molecular oxygen is catalyzed by the oxygen-evolving complex (OEC) in Photosystem II (PS II). This multi-electron, multi-proton catalysis requires the transport of two water molecules to and four protons from the OEC. A high-resolution 1.89 Å structure obtained by averaging all the S states and refining the data of various time points during the S 2 to S 3 transition has provided better visualization of the potential pathways for substrate water insertion and proton release. Our results indicate that the O1 channel is the likely water intake pathway, and the Cl1 channel is the likely proton release pathway based on the structural rearrangements of water molecules and amino acid side chains along these channels. In particular in the Cl1 channel, we suggest that residue D1-E65 serves as a gate for proton transport by minimizing the back reaction. The results show that the water oxidation reaction at the OEC is well coordinated with the amino acid side chains and the H-bonding network over the entire length of the channels, which is essential in shuttling substrate waters and protons.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS1994

Alpha-helical hydrophobic polypeptides form proton-selective channels in lipid bilayers

Proton translocation is important in membrane-mediated processes such as ATP-dependent proton pumps, ATP synthesis, bacteriorhodopsin, and cytochrome oxidase function. The fundamental mechanism, however, is poorly understood. To test the theoretical possibility that bundles of hydrophobic alpha-helices could provide a low energy pathway for ion translocation through the lipid bilayer, polyamino acids were incorporated into extruded liposomes and planar lipid membranes, and proton translocation was measured. Liposomes with incorporated long-chain poly-L-alanine or poly-L-leucine were found to have proton permeability coefficients 5 to 7 times greater than control liposomes, whereas short-chain polyamino acids had relatively little effect. Potassium permeability was not increased markedly by any of the polyamino acids tested. Analytical thin layer chromatography measurements of lipid content and a fluorescamine assay for amino acids showed that there were approximately 135 polyleucine or 65 polyalanine molecules associated with each liposome. Fourier transform infrared spectroscopy indicated that a major fraction of the long-chain hydrophobic peptides existed in an alpha-helical conformation. Single-channel recording in both 0.1 N HCl and 0.1 M KCl was also used to determine whether proton-conducting channels formed in planar lipid membranes (phosphatidylcholine/phosphatidylethanolamine, 1:1). Poly-L-leucine and poly-L-alanine in HCl caused a 10- to 30-fold increase in frequency of conductive events compared to that seen in KCl or by the other polyamino acids in either solution. This finding correlates well with the liposome observations in which these two polyamino acids caused the largest increase in membrane proton permeability but had little effect on potassium permeability. Poly-L-leucine was considerably more conductive than poly-L-alanine due primarily to larger event amplitudes and, to a lesser extent, a higher event frequency. Poly-L-leucine caused two populations of conductive events, one in the 0.1-0.5 pA range, and one in the 1.0-5.0 pA range, whereas nearly all events caused by poly-L-alanine were in the 0.1-0.5 pA range at an applied voltage of +60 mV. The channel-like activity appeared to switch between conductive and nonconductive states, with most open-times in the range of 50-200 ms. We conclude that hydrophobic polyamino acids produce proton-conducting defects in lipid bilayers that may be used to model functional proton channels in biological membranes.

NASA Discipline Exobiology↗
DOE OSTI2022

Modeling ammonia-fueled co-flow dual-channel protonic-ceramic fuel cells

This paper reports the model development for a dual-channel protonic-ceramic fuel cell (PCFC) operating on ammonia fuel. The model considers the coupled interactions of several physical and chemical processes, including three-dimensional heat conduction within the bipolar plates and the membrane-electrode assembly (MEA), one-dimensional flow within the fuel and air channels, detailed heterogeneous catalytic reactions within the porous composite anode structure, Butler–Volmer representation of the charge-transfer chemistry, and Nernst–Planck transport of three charged defects (protons, oxygen vacancies, and small polarons) within the dense electrolyte membrane. The membrane-electrode assembly is composed of a Ni-BCZYYb (BaCe 0.7 Zr 0.1 Y 0.1 Yb 0.1 O 3-δ ) anode, a BCZYYb electrolyte membrane, and a BCFZY (BaCo 0.4 Fe 0.4 Zr 0.1 Y 0.1 O 3-δ ) cathode. Chemical and physical parameters for the MEA model are established using previously published button-cell data. One aspect of the study is to investigate the partial ammonia decomposition upstream of the fuel cell. Such fuel cracking increases the H 2 content of the fuel entering the PCFC, which may have benefits. However, endothermic ammonia pyrolysis within the composite anode structure assists with thermal control of the cell. The dual-channel model can be considered as the unit cell of a full fuel-cell stack.

25 ENERGY STORAGE↗
DOE OSTI2023

Measurement of single top-quark production in the s-channel in proton–proton collisions at $\sqrt{s}$ = 13 TeV with the ATLAS detector

A measurement of single top-quark production in the s-channel is performed in proton–proton collisions at a centre-of-mass energy of 13 TeV with the ATLAS detector at the CERN Large Hadron Collider. The dataset corresponds to an integrated luminosity of 139 fb –1 . The analysis is performed on events with an electron or muon, missing transverse momentum and exactly two $b$-tagged jets in the final state. A discriminant based on matrix element calculations is used to separate single-top-quark s-channel events from the main background contributions, which are top-quark pair production and $W$-boson production in association with jets. The observed (expected) signal significance over the background-only hypothesis is 3.3 (3.9) standard deviations, and the measured cross-section is $σ$ = ${8.2}_{-2.9}^{+3.5}$ pb, consistent with the Standard Model prediction of $σ^{SM}$ = ${10.32}_{–0.36}^{+0.40}$ pb.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗
DOE OSTI2020

Cryo-EM and MD infer water-mediated proton transport and autoinhibition mechanisms of V o complex

Rotary vacuolar adenosine triphosphatases (V-ATPases) drive transmembrane proton transport through a Vo proton channel subcomplex. Despite recent high-resolution structures of several rotary ATPases, the dynamic mechanism of proton pumping remains elusive. Here, we determined a 2.7-Å cryo–electron microscopy (cryo-EM) structure of yeast V o proton channel in nanodisc that reveals the location of ordered water molecules along the proton path, details of specific protein-lipid interactions, and the architecture of the membrane scaffold protein. Moreover, we uncover a state of V o that shows the c-ring rotated by ~14°. Molecular dynamics simulations demonstrate that the two rotary states are in thermal equilibrium and depict how the protonation state of essential glutamic acid residues couples water-mediated proton transfer with c-ring rotation. Our cryo-EM models and simulations also rationalize a mechanism for inhibition of passive proton transport as observed for free V o that is generated as a result of V-ATPase regulation by reversible disassembly in vivo.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Constraints on anomalous Higgs boson couplings from its production and decay using the WW channel in proton–proton collisions at $\sqrt{s} = 13~\text {TeV}$

A study of the anomalous couplings of the Higgs boson to vector bosons, including ${\textit{CP}}$-violation effects, has been conducted using its production and decay in the WW channel. This analysis is performed on proton–proton collision data collected with the CMS detector at the CERN LHC during 2016–2018 at a center-of-mass energy of 13 TeV, and corresponds to an integrated luminosity of 138$\,\text {fb}^{-1}$. The different-flavor dilepton $({\textrm{e}} {{\upmu }})$ final state is analyzed, with dedicated categories targeting gluon fusion, electroweak vector boson fusion, and associated production with a W or Z boson. Kinematic information from associated jets is combined using matrix element techniques to increase the sensitivity to anomalous effects at the production vertex. A simultaneous measurement of four Higgs boson couplings to electroweak vector bosons is performed in the framework of a standard model effective field theory. All measurements are consistent with the expectations for the standard model Higgs boson and constraints are set on the fractional contribution of the anomalous couplings to the Higgs boson production cross section.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗
NASA NTRS2016

Two Exceptions in the Large SEP Events of Solar Cycles 23 and 24

We discuss our findings from a survey of all large solar energetic particle (SEP) events of Solar Cycles 23 and 24, i.e. the SEP events where the intensity of greater than 10 megaelectronvolts protons observed by GOES (Geostationary Operational Environmental Satellite) was greater than 10 proton flux units. In our previous work (Gopalswamy et al. in Geophys.Res.Lett. 41, 2673, 2014) we suggested that ground level enhancements (GLEs) in Cycles 23 and 24 also produce an intensity increase in the GOES greater than 700 megaelectronvolts proton channel. Our survey, now extended to include all large SEP events of Cycle 23, confirms this to be true for all but two events: i) the GLE of 6 May 1998 (GLE57) for which GOES did not observe enhancement in greater than 700 megaelectronvolts protons intensities and ii) a high-energy SEP event of 8 November 2000, for which GOES observed greater than 700 megaelectronvolts protons but no GLE was recorded. Here we discuss these two exceptions. We compare GLE57 with other small GLEs, and the 8 November 2000 SEP event with those that showed similar intensity increases in the GOES greater than 700 megaelectronvolts protons but produced GLEs. We find that, because GOES greater than 700 megaelectronvolts proton intensity enhancements are typically small for small GLEs, they are difficult to discern near solar minima due to higher background. Our results also support that GLEs are generally observed when shocks of the associated coronal mass ejections (CMEs) form at heights 1.2-1.93 solar radii [R (sub solar)] and when the solar particle release occurs between 2-6 solar radii [R (sub solar)]. Our secondary findings support the view that the nose region of the CME-shock may be accelerating the first-arriving GLE particles and the observation of a GLE is also dependent on the latitudinal connectivity of the observer to the CME-shock nose. We conclude that the GOES greater than 700 megaelectronvolts proton channel can be used as an indicator of GLEs excluding some rare exceptions, such as those discussed here.

Thakur, N.↗
DOE OSTI2020

Extraction of Beam-Spin Asymmetries from the Hard Exclusive π + Channel off Protons in a Wide Range of Kinematics

We have measured beam-spin asymmetries to extract the $\sin\phi$ moment $A_{LU}^{\sin\phi}$ from the hard exclusive $\vec{e} p \to e^\prime n \pi^+$ reaction above the resonance region, for the first time with nearly full coverage from forward to backward angles in the center-of-mass. The $A_{LU}^{\sin\phi}$ moment has been measured up to 6.6 GeV$^{2}$ in $-t$, covering the kinematic regimes of Generalized Parton Distributions (GPD) and baryon-to-meson Transition Distribution Amplitudes (TDA) at the same time. The experimental results in very forward kinematics demonstrate the sensitivity to chiral-odd and chiral-even GPDs. In very backward kinematics where the TDA framework is applicable, we found $A_{LU}^{\sin\phi}$ to be negative, while a sign change was observed near 90$^\circ$ in the center-of-mass. The unique results presented in this paper will provide critical constraints to establish reaction mechanisms that can help to further develop the GPD and TDA frameworks.

72 PHYSICS OF ELEMENTARY PARTICLES AND FIELDS↗
DOE OSTI2022

Gating choreography and mechanism of the human proton-activated chloride channel $\mathrm{ASOR}$

The proton-activated chloride channel ASOR (TMEM206/PAC) permeates anions across cellular membranes in response to acidification, thereby enhancing acid-induced cell death and regulating endocytosis. The molecular mechanisms of pH-dependent control are not understood, in part because structural information for an activated conformation of ASOR is lacking. Here, we reconstitute function from purified protein and present a 3.1-Å-resolution cryo–electron microscopy structure of human ASOR at acidic pH in an activated conformation. The work contextualizes a previous acidic pH structure as a desensitized conformation. Combined with electrophysiological studies and high-resolution structures of resting and desensitized states, the work reveals mechanisms of proton sensing and ion pore gating. Clusters of extracellular acidic residues function as pH sensors and coalesce when protonated. Ensuing conformational changes induce metamorphosis of transmembrane helices to fashion an ion conduction pathway unique to the activated conformation. The studies identify a new paradigm of channel gating in this ubiquitous ion channel.

59 BASIC BIOLOGICAL SCIENCES↗
NASA NTRS2003

Membrane-Based Functions in the Origin of Cellular Life

How simple membrane peptides performed such essential proto-cellular functions as transport of ions and organic matter across membranes separating the interior of the cell from the environment, capture and utilization of energy, and transduction of environmental signals, is a key question in protobiological evolution. On the basis of detailed, molecular-level computer simulations we investigate how these peptides insert into membranes, self-assemble into higher-order structures and acquire functions. We have studied the insertion of an a-helical peptide containing leucine (L) and serine (S) of the form (LSLLLSL)S into a model membrane. The transmembrane state is metastable, and approximately 15 kcal/mol is required to insert the peptide into the membrane. Investigations of dimers formed by (LSLLLSL)S and glycophorin A demonstrate how the favorable free energy of helix association can offset the unfavorable free energy of insertion, leading to self- assembly of peptide helices in the membrane. An example of a self-assembled structure is the tetrameric transmembrane pore of the influenza virus M2 protein, which is an efficient and selective voltage-gated proton channel. Our simulations explain the gating mechanism and provide guidelines how to reengineering the channel to act as a simple proton pump. In general, emergence of integral membrane proteins appears to be quite feasible and may be easier to envision than the emergence of water-soluble proteins.

Wilson, Michael A.↗
NASA NTRS2003

Membrane peptides and their role in protobiological evolution

How simple membrane peptides performed such essential protocellular functions as transport of ions and organic matter across membranes separating the interior of the cell from the environment, capture and utilization of energy, and transduction of environmental signals, is a key question in protobiological evolution. On the basis of detailed, molecular-level computer simulations we explain how these peptides fold at water-membrane interfaces, insert into membranes, self-assemble into higher-order structures and acquire functions. We have investigated the interfacial behavior and folding of several peptides built of leucine and glutamine residues and have demonstrated that many of them tend to adopt ordered structures. Further, we have studied the insertion of an alpha-helical peptide containing leucine (L) and serine (S) of the form (LSLLLSL)3 into a model membrane. The transmembrane state is metastable, and approximately 15 kcal mol(-1) is required to insert the peptide into the membrane. Investigations of dimers formed by (LSLLLSL)3 and glycophorin A demonstrate how the favorable free energy of helix association can offset the unfavorable free energy of insertion, leading to self-assembly of peptide helices in the membrane. An example of a self-assembled structure is the tetrameric transmembrane pore of the influenza virus M2 protein, which is an efficient and selective voltage-gated proton channel. Our simulations explain the gating mechanism and provide guidelines how to re-engineer the channel to act as a simple proton pump. In general, emergence of integral membrane proteins appears to be quite feasible and may be easier to envision than the emergence of water-soluble proteins.

Models, Chemical↗
DOE OSTI2023

Inhibition of the proton-activated chloride channel PAC by PIP 2

Proton-activated chloride (PAC) channel is a ubiquitously expressed pH-sensing ion channel, encoded by PACC1 (TMEM206). PAC regulates endosomal acidification and macropinosome shrinkage by releasing chloride from the organelle lumens. It is also found at the cell surface, where it is activated under pathological conditions related to acidosis and contributes to acid-induced cell death. However, the pharmacology of the PAC channel is poorly understood. Here, we report that phosphatidylinositol (4,5)-bisphosphate (PIP 2 ) potently inhibits PAC channel activity. We solved the cryo-electron microscopy structure of PAC with PIP 2 at pH 4.0 and identified its putative binding site, which, surprisingly, locates on the extracellular side of the transmembrane domain (TMD). While the overall conformation resembles the previously resolved PAC structure in the desensitized state, the TMD undergoes remodeling upon PIP 2 -binding. Structural and electrophysiological analyses suggest that PIP 2 inhibits the PAC channel by stabilizing the channel in a desensitized-like conformation. Our findings identify PIP 2 as a new pharmacological tool for the PAC channel and lay the foundation for future drug discovery targeting this channel.

59 BASIC BIOLOGICAL SCIENCES↗