scholarly journals Membrane transporter dimerization driven by differential lipid solvation energetics of dissociated and associated states

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Rahul Chadda ◽  
Nathan Bernhardt ◽  
Elizabeth G Kelley ◽  
Susana C M Teixeira ◽  
Kacie Griffith ◽  
...  
Keyword(s):  
Free Energy ◽  
Short Chain ◽  
Membrane Properties ◽  
Global Changes ◽  
Water Penetration ◽  
Low Concentrations ◽  
Solvent Environment ◽  
Lipid Solvent ◽  
Association Equilibria ◽  
Membrane Defect

Over two-thirds of integral membrane proteins of known structure assemble into oligomers. Yet, the forces that drive the association of these proteins remain to be delineated, as the lipid bilayer is a solvent environment that is both structurally and chemically complex. In this study we reveal how the lipid solvent defines the dimerization equilibrium of the CLC-ec1 Cl-/H+ antiporter. Integrating experimental and computational approaches, we show that monomers associate to avoid a thinned-membrane defect formed by hydrophobic mismatch at their exposed dimerization interfaces. In this defect, lipids are strongly tilted and less densely packed than in the bulk, with a larger degree of entanglement between opposing leaflets and greater water penetration into the bilayer interior. Dimerization restores the membrane to a near-native state and therefore, appears to be driven by the larger free-energy cost of lipid solvation of the dissociated protomers. Supporting this theory, we demonstrate that addition of short-chain lipids strongly shifts the dimerization equilibrium towards the monomeric state, and show that the cause of this effect is that these lipids preferentially solvate the defect. Importantly, we show that this shift requires only minimal quantities of short-chain lipids, with no measurable impact on either the macroscopic physical state of the membrane or the protein's biological function. Based on these observations, we posit that free-energy differentials for local lipid solvation define membrane-protein association equilibria. With this, we argue that preferential lipid solvation is a plausible cellular mechanism for lipid regulation of oligomerization processes, as it can occur at low concentrations and does not require global changes in membrane properties.

scholarly journals Dimerization of a membrane transporter is driven by differential energetics of lipid solvation of dissociated and associated states

2020 ◽  
Author(s):  
Rahul Chadda ◽  
Nathan Bernhardt ◽  
Elizabeth G. Kelley ◽  
Susana C. M. Teixeira ◽  
Kacie Griffith ◽  
...  
Keyword(s):  
Membrane Protein ◽  
Physical State ◽  
Physical Mechanism ◽  
Molecular Level ◽  
Membrane Transporter ◽  
Computational Approaches ◽  
Solvent Environment ◽  
Lipid Solvent ◽  
Association Equilibria ◽  
Membrane Defect

ABSTRACTOver two-thirds of membrane proteins of known structure assemble into oligomers. Yet, the forces that drive the association of these proteins in the membrane remain to be delineated, as the lipid bilayer is a solvent environment that is both structurally and chemically complex. In this study we reveal how the lipid solvent defines the dimerization equilibrium of the CLC-ec1 Cl-/H+ antiporter. Integrating experimental and computational approaches, we show that monomers associate to avoid an energetic penalty for solvating a thinned-membrane defect caused by their exposed dimerization interfaces. Supporting this theory, we demonstrate that this penalty is drastically reduced with minimal amounts of short-chain lipids, which stabilize the monomeric state by preferentially solvating the defect rather than altering the physical state of the membrane. We thus posit that the energy differentials for local lipid-solvation define membrane-protein association equilibria, and describe a molecular-level physical mechanism for lipid regulation of such processes in biological conditions.

scholarly journals The enzymology of short-chain fatty acyl-coenzyme A synthetase from seeds of Pinus radiata. Kinetic studies and a proposed reaction mechanism

1974 ◽  
Vol 137 (3) ◽  
pp. 435-442 ◽  
Author(s):  
Owen A. Young ◽  
John W. Anderson
Keyword(s):  
Fatty Acid ◽  
Pinus Radiata ◽  
Kinetic Studies ◽  
Single Species ◽  
Competitive Inhibitor ◽  
Fatty Acyl ◽  
Short Chain ◽  
Low Concentrations ◽  
High Concentrations ◽  
Acyl Coenzyme A

1. Short-chain fatty acyl-CoA synthetase from seeds of Pinus radiata was examined by acetate- and propionate-dependent PPi–ATP exchange. Reaction mixtures came to equilibrium almost instantly as judged by rates of exchange and analysis of an incubation mixture. 2. The activity of the enzyme was correlated with the concentration of MgP2O72- but not with the concentration of Mg2+, as judged by PPi–ATP exchange and fatty acyl AMP-dependent synthesis of ATP in the presence of PPi. In PPi–ATP exchange assays, no clear relationship between activity and any single species of ATP was apparent. 3. High concentrations of fatty acid inhibited PPi–ATP exchange. PPi–dATP exchange was less than PPi–ATP exchange at low concentrations of fatty acid, but at higher concentrations PPi–dATP exchange exceeded PPi–ATP exchange. The rate of synthesis of fatty acyl-CoA in the presence of dATP was less than with ATP. 4. ATP and propionate inhibited the synthesis of ATP from propionyl-AMP and PPi. The inhibition by ATP was competitive with respect to propionyl-AMP and non-competitive with respect to PPi. The inhibition by propionate was non-competitive with respect to propionyl-AMP and PPi. 5. AMP was a competitive inhibitor of propionyl-AMP-dependent synthesis of ATP and competitively inhibited propionate-dependent PPi–ATP exchange when ATP was the variable substrate. 6. It was concluded that the first partial reaction catalysed by the enzyme is ordered; ATP is the first substrate to react with the enzyme and PPi is probably the only product released.

Increased vulnerability to inducible atrial fibrillation caused by partial cellular uncoupling with heptanol

2002 ◽  
Vol 283 (3) ◽  
pp. H1116-H1122 ◽  
Author(s):  
Toshihiko Ohara ◽  
Zhilin Qu ◽  
Moon-Hyoung Lee ◽  
Keiko Ohara ◽  
Chikaya Omichi ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Conduction Block ◽  
Membrane Properties ◽  
Maximal Velocity ◽  
Epicardial Surface ◽  
Low Concentrations ◽  
Before And After ◽  
Rapid Pacing ◽  
Action Potential Duration Restitution ◽  
Over Time

We hypothesized that partial cellular uncoupling produced by low concentrations of heptanol increases the vulnerability to inducible atrial fibrillation (AF). The epicardial surface of 12 isolated-perfused canine left atria was optically mapped before and after 1–50 μM heptanol infusion. At baseline, no sustained (>30 s) AF could be induced in any of the 12 tissues. However, after 2 μM heptanol infusion, sustained AF was induced in 9 of 12 tissues ( P < 0.001). Heptanol >5 μM caused loss of 1:1 capture during rapid pacing, causing no AF to be induced. AF was initiated by conduction block across the fiber leading to reentry, which broke up after one to two rotations into two to four independent wavelets that sustained the AF. Heptanol at 2 μM had no effect on the cellular action potential duration restitution or on the maximal velocity rate over time of the upstroke. The effects of heptanol were reversible. We conclude that partial cellular uncoupling by heptanol without changing atrial active membrane properties promotes wavebreak, reentry, and AF during rapid pacing.

scholarly journals Thermodynamics of Microbial Growth Coupled to Metabolism of Glucose, Ethanol, Short-Chain Organic Acids, and Hydrogen

2011 ◽  
Vol 77 (5) ◽  
pp. 1907-1909 ◽  
Author(s):  
Eric E. Roden ◽  
Qusheng Jin
Keyword(s):  
Free Energy ◽  
Organic Acids ◽  
Linear Relationship ◽  
Microbial Growth ◽  
Growth Yield ◽  
Short Chain ◽  
Redox Metabolism ◽  
Sedimentary Environments ◽  
Fermentative Metabolism ◽  
Aerobic And Anaerobic

ABSTRACTA literature compilation demonstrated a linear relationship between microbial growth yield and the free energy of aerobic and anaerobic (respiratory and/or fermentative) metabolism of glucose, ethanol, formate, acetate, lactate, propionate, butyrate, and H2. This relationship provides a means to estimate growth yields for modeling microbial redox metabolism in soil and sedimentary environments.

scholarly journals Designing hypercitizenship methodologically

2014 ◽  
Vol 5 (1) ◽  
pp. 2 ◽  
Author(s):  
Andrea Pitasi
Keyword(s):  
Free Energy ◽  
Global Changes ◽  
Entropy Coding ◽  
Four Dimensions ◽  
Entrepreneurial Society

This paper is essentially epistemological and methodological and is aimed at designing the hypercitizen methodological toolkit. It is not merely through an indicator based approach but also on a modelling based approach and a metatheoretical one (Stepanic et al., 2005: 858). Conceptually, it evolves by reframing the key global changes of our times under the emer-gence of hypercitizenship from a multidimensional convergence among different kinds of citizenship Pitasi, 2013; Pitasi- Angrisani , 2013): cosmopolitan (Beck, 2006), scientific (Nowotny, 2008), societarian (Donati, 1993), entrepreneurial (I evolved by reinterpreting Audretsch, 2007 who, properly, copes with the “entrepreneurial society” not the entrepre-neurial citizenship).The four dimensions are shaped systemically (Luhmann, 1990, 1997) through a social free energy/social entropy coding (Stepanic et al., 2005: 860). 

scholarly journals Comparison between surface and volumetric properties of short-chain alcohols and some classical surfactants

2016 ◽  
Vol 71 (1) ◽  
pp. 1 ◽  
Author(s):  
Magdalena Bielawska ◽  
Anna Zdziennicka ◽  
Bronisław Jańczuk
Keyword(s):  
Free Energy ◽  
Aqueous Solutions ◽  
Chemical Potential ◽  
Standard Free Energy ◽  
Dynamic Surface Tension ◽  
Short Chain ◽  
Critical Aggregation Concentration ◽  
Free Energy Of Adsorption ◽  
Dynamic Surface ◽  
Air Interface

<p>Measurements of the dynamic surface tension of the aqueous solutions of methanol, ethanol, propanol, CTAB and SDDS at their given concentrations were made. From the obtained results and the literature data it was concluded that the adsorption of short-chain alcohols at the water-air interface is somewhat similar to that of classical surfactants. For that reason the relationship between the Gibbs standard free energy of adsorption of short-chain alcohols and classical surfactants at that interface was established. The correlation between the chemical potential of mixing of alcohols and surfactants was also analysed. This analysis concerned the critical aggregation concentration (CAC) of alcohols and the critical micelle concentration (CMC) of surfactants. The chemical potential of surfactant mixing was calculated from the literature CMC data for the homologous series of alkyl sulfates, alkyl sulfonates, alkyl ammonium chlorides, alkyl trimethylammonium bromides, and alkyl pyridinium bromides. The influence of the hydrophobic chain length of alcohol and surfactant molecules on the Gibbs standard free energy of their adsorption at the water-air interface and their chemical potential of mixing were considered. It appeared that there is a linear dependence between these thermodynamic functions and the number of carbon atoms increased by 1 in the hydrocarbon chains of these compounds. This confirms clearly our conclusion that the behaviour of short-chain alcohols and classical surfactants at the water-air interface and in the bulk phase of aqueous solutions is similar. </p>

scholarly journals How does the Earth system generate and maintain thermodynamic disequilibrium and what does it imply for the future of the planet?

2012 ◽  
Vol 370 (1962) ◽  
pp. 1012-1040 ◽  
Author(s):  
Axel Kleidon
Keyword(s):  
Free Energy ◽  
Human Activity ◽  
Climate Models ◽  
Net Primary Productivity ◽  
Second Law Of Thermodynamics ◽  
Global Changes ◽  
Earth System ◽  
Geochemical Composition ◽  
The Earth ◽  
The Future

The Earth's chemical composition far from chemical equilibrium is unique in our Solar System, and this uniqueness has been attributed to the presence of widespread life on the planet. Here, I show how this notion can be quantified using non-equilibrium thermodynamics. Generating and maintaining disequilibrium in a thermodynamic variable requires the extraction of power from another thermodynamic gradient, and the second law of thermodynamics imposes fundamental limits on how much power can be extracted. With this approach and associated limits, I show that the ability of abiotic processes to generate geochemical free energy that can be used to transform the surface–atmosphere environment is strongly limited to less than 1 TW. Photosynthetic life generates more than 200 TW by performing photochemistry, thereby substantiating the notion that a geochemical composition far from equilibrium can be a sign for strong biotic activity. Present-day free energy consumption by human activity in the form of industrial activity and human appropriated net primary productivity is of the order of 50 TW and therefore constitutes a considerable term in the free energy budget of the planet. When aiming to predict the future of the planet, we first note that since global changes are closely related to this consumption of free energy, and the demands for free energy by human activity are anticipated to increase substantially in the future, the central question in the context of predicting future global change is then how human free energy demands can increase sustainably without negatively impacting the ability of the Earth system to generate free energy. This question could be evaluated with climate models, and the potential deficiencies in these models to adequately represent the thermodynamics of the Earth system are discussed. Then, I illustrate the implications of this thermodynamic perspective by discussing the forms of renewable energy and planetary engineering that would enhance the overall free energy generation and, thereby ‘empower’ the future of the planet.

scholarly journals Effects of lipid composition on membrane distribution and permeability of natural quinones

2019 ◽  
Author(s):  
Murilo Hoias Teixeira ◽  
Guilherme Menegon Arantes
Keyword(s):  
Free Energy ◽  
Lipid Composition ◽  
Proton Translocation ◽  
Acyl Chain ◽  
Free Energy Calculations ◽  
Free Energy Barrier ◽  
Water Penetration ◽  
Amphiphilic Molecules ◽  
Dynamics Simulations

ABSTRACTNatural quinones are amphiphilic molecules that function as mobile charge carriers in biological energy transduction. Their distribution and permeation across membranes are important for binding to enzymatic complexes and for proton translocation. Here, we employ molecular dynamics simulations and free energy calculations with a carefully calibrated classical force-field to probe quinone distribution and permeation in a multicomponent bilayer trying to mimic the composition of membranes involved in bioenergetic processes. Ubiquinone, ubiquinol, plastoquinone and menaquinone molecules with short and long isoprenoid tails are simulated. We find that water penetration increases considerably in the less ordered and porous bilayer formed by di-linoleoyl (18:2) phospholipids, resulting in a lower free energy barrier for quinone permeation and faster transversal diffusion. In equilibrium, quinone and quinol heads localize preferentially near lipid glycerol groups, but do not perform specific contacts with lipid polar heads. Quinone distribution is not altered significantly by the quinone head, tail and lipid composition in comparison to a single-component bilayer. This study highlights the role of acyl chain unsaturation for molecular permeation and transversal diffusion across biological membranes.

scholarly journals Global transformation of erythrocyte properties via engagement of an SH2-like sequence in band 3

2016 ◽  
Vol 113 (48) ◽  
pp. 13732-13737 ◽  
Author(s):  
Estela Puchulu-Campanella ◽  
Francesco M. Turrini ◽  
Yen-Hsing Li ◽  
Philip S. Low
Keyword(s):  
Band 3 ◽  
Transport Proteins ◽  
Membrane Properties ◽  
Erythrocyte Membranes ◽  
Global Changes ◽  
Intact Cells ◽  
Sh2 Domains ◽  
Conserved Sequence ◽  
Anion Transporter ◽  
Membrane Spanning

Src homology 2 (SH2) domains are composed of weakly conserved sequences of ∼100 aa that bind phosphotyrosines in signaling proteins and thereby mediate intra- and intermolecular protein–protein interactions. In exploring the mechanism whereby tyrosine phosphorylation of the erythrocyte anion transporter, band 3, triggers membrane destabilization, vesiculation, and fragmentation, we discovered a SH2 signature motif positioned between membrane-spanning helices 4 and 5. Evidence that this exposed cytoplasmic sequence contributes to a functional SH2-like domain is provided by observations that: (i) it contains the most conserved sequence of SH2 domains, GSFLVR; (ii) it binds the tyrosine phosphorylated cytoplasmic domain of band 3 (cdb3-PO4) withKd= 14 nM; (iii) binding of cdb3-PO4to erythrocyte membranes is inhibited both by antibodies against the SH2 signature sequence and dephosphorylation of cdb3-PO4; (iv) label transfer experiments demonstrate the covalent transfer of photoactivatable biotin from isolated cdb3-PO4(but not cdb3) to band 3 in erythrocyte membranes; and (v) phosphorylation-induced binding of cdb3-PO4to the membrane-spanning domain of band 3 in intact cells causes global changes in membrane properties, including (i) displacement of a glycolytic enzyme complex from the membrane, (ii) inhibition of anion transport, and (iii) rupture of the band 3–ankyrin bridge connecting the spectrin-based cytoskeleton to the membrane. Because SH2-like motifs are not retrieved by normal homology searches for SH2 domains, but can be found in many tyrosine kinase-regulated transport proteins using modified search programs, we suggest that related cases of membrane transport proteins containing similar motifs are widespread in nature where they participate in regulation of cell properties.

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