Low-temperature deuterium NMR spectroscopy of phospholipid bilayers containing docosahexaenoyl (22:6.omega.3) chains

Barry, Judith; Trouard, Theodore P.; Salmon, Amir; Brown, Michael F.

doi:10.1021/bi00098a016

Cited by 44 publications

(58 citation statements)

References 42 publications

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“…The intensity difference ⌬S between the two spectra can be directly related to the dipolar coupling of each spin pair, from which the internuclear distance can be deduced (28). The first group of experiments (1Ј-13 C-observe) was aimed at determining the location of the anandamide headgroup, and we observed positive effects (⌬S Ն 0) in both the 1Ј-13 C-observe, 31 P-dephased (1Ј-13 C/ 31 P) and the 1Ј-13 Cobserve, 2Ј-2 H 2 -dephased (1Ј-13 C/2Ј-2 H 2 ) experiments. However, no effects (⌬S ϭ 0) were observed in the 1Ј-13 C/7Ј-2 H 2 REDOR experiment.…”

Section: Resultsmentioning

confidence: 85%

“…It is interesting to compare our findings with work related to the structural properties of unsaturated membrane lipids because anandamide is derived from polyunsaturated phospholipids. Recent studies involving unsaturated diaryl phospholipids such as 1-palmitoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine (PDPC) and 1-stearoyl-2-docosahexaenoyl-sn-glycero-3-phosphocholine (SDPC) show that in the gel L ␤ phase, both the saturated and the polyunsaturated chains adopt the all-trans and extended (angle iron or helical) conformations, respectively (31,32). A similar result was obtained from studies on PDPC and 1-stearoyl-2-arachidonoyl-sn-glycero-3-phosphocholine (SAPC) molecules in the liquid crystalline L ␣ phase using either computational or 2 H NMR approaches (33,34).…”

Section: Dynamic Properties Of Anandamide In the Dppc Liquid Crystallmentioning

confidence: 99%

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The Conformation, Location, and Dynamic Properties of the Endocannabinoid Ligand Anandamide in a Membrane Bilayer

Tian

Guo

Yao

et al. 2005

Journal of Biological Chemistry

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The endogenous cannabinoid ligand anandamide is biosynthesized from membrane phospholipid precursors and is believed to reach its sites of action on the CB1 and CB2 receptors through fast lateral diffusion within the cell membrane. To gain a better insight on the stereochemical features of its association with the cell membrane and its interaction with the cannabinoid receptors, we have studied its conformation, location, and dynamic properties in a dipalmitoylphosphatidylcholine multilamellar model membrane bilayer system. By exploiting the bilayer lattice as an internal threedimensional reference grid, the conformation and location of anandamide were determined by measuring selected inter-and intramolecular distances between strategically introduced isotopic labels using the rotational echo double resonance (REDOR) NMR method. A molecular model was proposed to represent the structural features of our anandamide/lipid system and was subsequently used in calculating the multispin dephasing curves. Our results demonstrate that anandamide adopts an extended conformation within the membrane with its headgroup at the level of the phospholipid polar group and its terminal methyl group near the bilayer center. Parallel static 2 H NMR experiments further confirmed these findings and provided evidence that anandamide experiences dynamic properties similar to those of the membrane phospholipids and produces no perturbation to the bilayer. Our results are congruent with a hypothesis that anandamide approaches its binding site by laterally diffusing within one membrane leaflet in an extended conformation and interacts with a hydrophobic groove formed by helices 3 and 6 of CB1, where its terminal carbon is positioned close to a key cysteine residue in helix 6 leading to receptor activation.The membrane lipid bilayer is a ubiquitous molecular assembly into which are embedded a variety of proteins, natural hormones, and neurotransmitters. Accumulated evidence indicates that many fatty acid-derived lipophilic neurotransmitters are synthesized, stored, and degraded and also exert their functions within the lipid membrane (1, 2). Therefore, it has been suggested that the conformation, location, and orientation of the ligand in the membrane are critical in determining its ability to reach and interact productively with its site of action (3-5). Exploring the conformational and dynamic properties of these ligands in the membrane can lead to a better understanding of the molecular features involved in their interactions with the target proteins (6).N-Arachidonoylethanolamine (anandamide), initially isolated from mammalian brain, has been identified as an endogenous ligand for the two known G protein-coupled cannabinoid receptors (CB1 and CB2) (7). This endocannabinoid exerts its activity by modulating several physiological functions such as pain, cognition, and memory. Site-directed mutagenesis evidence has shown that the anandamide binding sites are embedded in the trans-membrane helices of the receptor (8, 9). This correlates wel...

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Section: Resultsmentioning

confidence: 85%

Section: Dynamic Properties Of Anandamide In the Dppc Liquid Crystallmentioning

confidence: 99%

The Conformation, Location, and Dynamic Properties of the Endocannabinoid Ligand Anandamide in a Membrane Bilayer

Tian

Guo

Yao

et al. 2005

Journal of Biological Chemistry

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“…(10) and (11). For a mixture of chains, the area factor q is the weighted sum, and the calculated value of 〈 A 〉 is the number-weighted average over the components, according to the theory of moments [100]. …”

Section: Relation Of Membrane Structure To Observables From Solid-mentioning

confidence: 99%

Elastic deformation and area per lipid of membranes: Atomistic view from solid-state deuterium NMR spectroscopy

Kinnun

Mallikarjunaiah

Petrache

et al. 2015

Biochimica et Biophysica Acta (BBA) - Biomembranes

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This article reviews the application of solid-state 2H nuclear magnetic resonance (NMR) spectroscopy for investigating the deformation of lipid bilayers at the atomistic level. For liquid-crystalline membranes, the average structure is manifested by the segmental order parameters (SCD) of the lipids. Solid-state 2H NMR yields observables directly related to the stress field of the lipid bilayer. The extent to which lipid bilayers are deformed by osmotic pressure is integral to how lipid-protein interactions affect membrane functions. Calculations of the average area per lipid and related structural properties are pertinent to bilayer remodeling and molecular dynamics (MD) simulations of membranes. To establish structural quantities, such as area per lipid and volumetric bilayer thickness, a mean-torque analysis of 2H NMR order parameters is applied. Osmotic stress is introduced by adding polymer solutions or by gravimetric dehydration, which are thermodynamically equivalent. Solid-state NMR studies of lipids under osmotic stress probe membrane interactions involving collective bilayer undulations, order-director fluctuations, and lipid molecular protrusions. Removal of water yields a reduction of the mean area per lipid, with a corresponding increase in volumetric bilayer thickness, by up to 20% in the liquid-crystalline state. Hydrophobic mismatch can shift protein states involving mechanosensation, transport, and molecular recognition by G-protein–coupled receptors. Measurements of the order parameters versus osmotic pressure yield the elastic area compressibility modulus and the corresponding bilayer thickness at an atomistic level. Solid-state 2H NMR thus reveals how membrane deformation can affect protein conformational changes within the stress field of the lipid bilayer.

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“…Solid-state 2 H NMR spectroscopy uses site-directed 2 H-labeling to investigate the local structure and dynamics of both proteins [19, 32, 33] and lipid bilayers [36–41]. In the case of membrane proteins, 2 H NMR provides orientational restraints (bond orientations), and when coupled with interatomic distance restraints it gives structural data analogous to solution NMR [19].…”

Section: Rhodopsin: Interface Between Experiments and Simulationmentioning

confidence: 99%

Molecular simulations and solid-state NMR investigate dynamical structure in rhodopsin activation

Mertz

Struts

Feller

et al. 2012

Biochimica et Biophysica Acta (BBA) - Biomembranes

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Rhodopsin has served as the primary model for studying G protein-coupled receptors (GPCRs)—the largest group in the human genome, and consequently a primary target for pharmaceutical development. Understanding the functions and activation mechanisms of GPCRs has proven to be extraordinarily difficult, as they are part of a complex signaling cascade and reside within the cell membrane. Although X-ray crystallography has recently solved several GPCR structures that may resemble the activated conformation, the dynamics and mechanism of rhodopsin activation continue to remain elusive. Notably solid-state 2H NMR spectroscopy provides key information pertinent to how local dynamics of the retinal ligand change during rhodopsin activation. When combined with molecular mechanics simulations of proteolipid membranes, a new paradigm for the rhodopsin activation process emerges. Experiment and simulation both suggest that retinal isomerization initiates the rhodopsin photocascade to yield not a single activated structure, but rather an ensemble of activated conformational states.

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Low-temperature deuterium NMR spectroscopy of phospholipid bilayers containing docosahexaenoyl (22:6.omega.3) chains

Cited by 44 publications

References 42 publications

The Conformation, Location, and Dynamic Properties of the Endocannabinoid Ligand Anandamide in a Membrane Bilayer

The Conformation, Location, and Dynamic Properties of the Endocannabinoid Ligand Anandamide in a Membrane Bilayer

Elastic deformation and area per lipid of membranes: Atomistic view from solid-state deuterium NMR spectroscopy

Molecular simulations and solid-state NMR investigate dynamical structure in rhodopsin activation

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