Deuteron Quadrupole Coupling Constants in Three Solid Deuterated Paraffin Hydrocarbons: C2D6, C4D10, C6D14

Burnett, L. J.; Müller, B. H.

doi:10.1063/1.1675758

Cited by 241 publications

(89 citation statements)

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“…42,43 Since the quadrupolar splitting (Δν q ) is related to the segmental order parameter, S CD , an increase in the Δν q is generally associated with an increase in the order of the system, while a decrease in Δν q is associated with a decrease in the order. the error which was set to 0.1 for R 1 and 1 for R 2 .…”

Section: Methodsmentioning

confidence: 99%

Membrane-Perturbing Properties of Two Arg-Rich Paddle Domains from Voltage-Gated Sensors in the KvAP and HsapBK K⁺ Channels

et al. 2012

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Voltage-gated K + channels are gated by displacement of basic residues located in the S4 helix that together with a part of the S3 helix, S3b, forms a "paddle" domain, whose position is altered by changes in the membrane potential modulating the open probability of the channel. Here, interactions between two paddle domains,KvAPp from the K v channel from Aeropyrum pernix and HsapBKp from the BK channel from Homo sapiens, and membrane models have been studied by spectroscopy.We show that both paddle domains induce calcein leakage in large unilamellar vesicles and we suggest that this leakage represent a general thinning of the bilayer making movement of the whole paddle domain plausible. That HsapBKp induces more leakage than KvAPp, may be explained by the presence of a Trp residue in HsapBKp. Trp residues generally promote localization to the hydrophilic/hydrophobic interface and disturb tight packing. In magnetically aligned bicelles KvAPp increases the order along the whole acyl chain, while HsapBKp affects the morphology, also indicating thatKvAPp adapts more to the lipid environment. Relaxation NMR measurements for HsapBKp show that overall the sequence has anisotropic motions. The S4 helix is wellstructured with restricted local motion, while the turn between S4 and S3b is more flexible and undergoes slow local motion. Our results indicate that the calcein leakage is related to the flexibility in this turn region. A possibility for HsapBKp to undergo structural transitions is also shown by relaxation NMR, which may be of importance for the gating mechanism. The aim of present study was to investigate how paddle domains from two different channels, the K v channel KvAP (from Aeropyrum pernix, GI:14601099) 2,3,6 and the BK channel HsapBK (from Homo sapiens, GI:2570854) 19 interact with membranes, to be able to draw general conclusions about the mechanism of gating and to be able to compare paddle domains from two different subtypes. We have previously determined the high-resolution NMR structure of the paddle-domain from HsapBK (HsapBKp, corresponding to HsapBK(233-260)) in DPC micelles. 19 The solution structure revealed a helix-turn-helix structure similar to the structure of the corresponding sequence in KvAP as determined by X-ray crystallography. 2,3,19 In the present study the interactions between the paddle domains from KvAP (KvAPp, corresponding to KvAP(112-146)) and from HsapBK (HsapBKp) and lipids were studied by fluorescence, circular dichroism (CD) and NMR spectroscopy. To investigate bilayer perturbation induced by the paddle domains, leakage of the fluorophore calcein from large unilamellar vesicles (LUVs) was monitored by fluorescence spectroscopy [20][21][22][23] . Circular dichroism was used to examine the lipiddependent structure induction, while deuterium NMR spectra of acyl-chain deuterated DMPC and DMPG in magnetically aligned bicelles were acquired to investigate the effects of the paddle domains on bilayer order and integrity. 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (...

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Section: Methodsmentioning

confidence: 99%

Membrane-Perturbing Properties of Two Arg-Rich Paddle Domains from Voltage-Gated Sensors in the KvAP and HsapBK K⁺ Channels

et al. 2012

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“…https://doi.org/10.1017/S0033583500002948 Downloaded from https:/www.cambridge.org/core. University of Basel Library, on 11 Jul 2017 at 10:12:49, subject to the Cambridge Deuterium magnetic resonance 377 be 170 kHz (Burnett & Muller, 1971) the order parameter 5 33 is readily evaluated from equation (45). In the case of C-D bonds the dominant axis of the axially symmetric field gradient tensor V P is identical with the C-D bond vector.…”

Section: > = D®(/r) S Z)$ (A/?) F< V" (47)mentioning

confidence: 99%

“…The second point of interest concerns the dynamical properties of the bilayer, that is the rate of segmental motions and the rate of diffusion of the lipids within each half layer. In terms of experimental parameters characteristic of magnetic resonance techniques Burnett & Muller (1971). % Kowalewski et al (1976).…”

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confidence: 99%

Deuterium magnetic resonance: theory and application to lipid membranes

Seelig

1977

Quart. Rev. Biophys.

1,268

1,041

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Proton and carbon-13 nmr spectra of unsonicated lipid bilayers and biological membranes are generally dominated by strong proton–proton and proton–carbon dipolar interactions. As a result the spectra contain a large number of overlapping resonances and are rather difficult to analyse. Nevertheless, important information on the structure and dynamic behaviour of lipid systems has been provided by these techniques (Wennerström & Lindblom, 1977).

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“…where A Q is the static deuterium quadrupolar constant (167 kHz for C-2 H bonds (30). S CD i profiles for the sn-1 chain of DPPC-d 62 were constructed according to the published assignments (28,29) and comparisons with specifically labeled phospholipids (31,32).…”

Section: Methodsmentioning

confidence: 99%

Cholesterol and Lipid Phases Influence the Interactions between Serotonin Receptor Agonists and Lipid Bilayers

Batchelor

Windle

Buchoux

et al. 2010

Journal of Biological Chemistry

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Solid state NMR techniques have been used to investigate the effect that two serotonin receptor 1a agonists (quipazine and LY-165,163) have on the phase behavior of, and interactions within, cholesterol/phosphocholine lipid bilayers. The presence of agonist, and particularly LY-165,163, appears to widen the phase transitions, an effect that is much more pronounced in the presence of cholesterol. It was found that both agonists locate close to the cholesterol, and their interactions with the lipids are modulated by the lipid phases. As the membrane condenses into mixed liquid-ordered/disordered phases, quipazine is pushed up toward the surface of the bilayer, whereas LY-165,163 moves deeper into the lipid chain region. In light of our results, we discuss the role of lipid/drug interactions on drug efficacy.The majority of drug targets are membrane proteins. Hence the interaction of a drug with the membrane is crucial for its efficacy. A high location probability in a particular part of a membrane and its orientation with respect to the membrane normal could well be relevant to how the drug is presented to the target protein's binding site (1, 2). Cholesterol-rich microdomains ("lipid rafts") add another layer of complexity because the lateral organization of the membrane could well affect the concentration of a drug close to its target protein. This possibility is backed up by the observation that many chemicals, including drugs that target serotonin receptors, preferentially localize into these domains (3-5). Meanwhile, the location and activity of some membrane proteins, particularly G-protein-coupled receptors, seem to be affected by domains (6). Therefore, it is easy to imagine that a drug's efficacy may be limited by it partitioning into a different membrane domain than its target receptor. Furthermore, it is clear that many membrane proteins are modulated by the properties of the surrounding lipids. Hence, a drug has the potential to regulate a protein by altering these properties (7). This raises the intriguing possibility of a class of drugs that, instead of directly targeting a protein, target the membrane in which the protein resides. This route of action was first proposed as early as 1899 as a possible mechanism for general anesthetics, when it was noted that the potency of an anesthetic correlated very strongly with olive oil/water partitioning (8), yet drugs affecting membrane proteins via lipid interactions, so called "membrane-lipid therapy," have only relatively recently been explored (7, 9, 10).Some simple lipid mixtures have been used as models for in vivo microdomains. A particularly well studied mixture consists of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) Proton NMR and specifically magic angle spinning-assisted nuclear Overhauser enhancement spectroscopy (MAS-NOESY) experiments have proven to be an excellent tool for investigating, with atomic resolution, the location of small molecules embedded in lipid membranes (17)(18)(19)(20). However, these studies have been limited to binary...

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Deuteron Quadrupole Coupling Constants in Three Solid Deuterated Paraffin Hydrocarbons: C2D6, C4D10, C6D14

Abstract: Deuteron quadrupole coupling in solid 3,6dichloropyridazined 2 and in antimony triphenyld 15

Cited by 241 publications

References 10 publications

Membrane-Perturbing Properties of Two Arg-Rich Paddle Domains from Voltage-Gated Sensors in the KvAP and HsapBK K⁺ Channels

Membrane-Perturbing Properties of Two Arg-Rich Paddle Domains from Voltage-Gated Sensors in the KvAP and HsapBK K⁺ Channels

Deuterium magnetic resonance: theory and application to lipid membranes

Cholesterol and Lipid Phases Influence the Interactions between Serotonin Receptor Agonists and Lipid Bilayers

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Deuteron Quadrupole Coupling Constants in Three Solid Deuterated Paraffin Hydrocarbons: C2D6, C4D10, C6D14

Abstract: Deuteron quadrupole coupling in solid 3,6dichloropyridazined 2 and in antimony triphenyld 15

Cited by 241 publications

References 10 publications

Membrane-Perturbing Properties of Two Arg-Rich Paddle Domains from Voltage-Gated Sensors in the KvAP and HsapBK K+ Channels

Membrane-Perturbing Properties of Two Arg-Rich Paddle Domains from Voltage-Gated Sensors in the KvAP and HsapBK K+ Channels

Deuterium magnetic resonance: theory and application to lipid membranes

Cholesterol and Lipid Phases Influence the Interactions between Serotonin Receptor Agonists and Lipid Bilayers

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Membrane-Perturbing Properties of Two Arg-Rich Paddle Domains from Voltage-Gated Sensors in the KvAP and HsapBK K⁺ Channels

Membrane-Perturbing Properties of Two Arg-Rich Paddle Domains from Voltage-Gated Sensors in the KvAP and HsapBK K⁺ Channels