Membrane Structure and Dynamics Studied with NMR Spectroscopy

Brown, Michael F.

doi:10.1007/978-1-4684-8580-6_7

Cited by 50 publications

(105 citation statements)

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“…Figure 1(a)-(c) shows representative 2 H NMR spectra from −100 kHz to +100 kHz for 11-Z-[9-C 2 H 3 ]-retinylidene rhodopsin in randomly oriented POPC membranes over a broad temperature range of 120 °C. Powder-type 2 H NMR spectra at temperatures of −30, −60, and −150 °C are similar and exhibit discontinuities at ∓19.5 kHz and ±39.0 kHz, due to the θ = 90° and θ = 0° orientations of the largest principal value of the electric field gradient (EFG) tensor relative to the main magnetic field 24 . Below the order-disorder phase transition temperature of POPC (T M = −4 °C) the 2 H NMR spectra correspond to the lipid gel state, where rotational and translational diffusion of both the protein 35 and lipids are diminished on the 2 H NMR time scale (< 10 μs for rotating methyls).…”

Section: Powder-type 2 H Nmr Spectra Of Retinal Bound To Rhodopsinmentioning

confidence: 99%

“…In this work, we used solid-state 2 H NMR spectroscopy 24,25 to address information about the retinal structure and dynamics in the dark and meta I states of the photoreceptor. We asked the following questions: (i) what is the basis for the phenomenal stability of 11-cis retinal in the dark state of rhodopsin?…”

Section: Introductionmentioning

confidence: 99%

“…Our work entailed total organic synthesis of 2 H isotopically-labeled retinals, together with biophysical 2 H NMR techniques and theoretical lineshape calculations 26 . Angular constraints were provided by 2 H NMR quadrupolar couplings 24,26,27 and distances from complementary rotational resonance 13 C NMR studies 25,28,29 . This approach is analogous to solution NMR, where residual dipolar couplings are used with distance restraints from nuclear Overhauser effect (NOE) spectroscopy.…”

Section: Introductionmentioning

confidence: 99%

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Structural Analysis and Dynamics of Retinal Chromophore in Dark and Meta I States of Rhodopsin from 2H NMR of Aligned Membranes

Struts

Salgado

Tanaka

et al. 2007

Journal of Molecular Biology

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134

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SummaryRhodopsin is a prototype for G protein-coupled receptors (GPCRs) that are implicated in many biological responses in humans. A site-directed 2 H NMR approach was used for structural analysis of retinal within its binding cavity in the dark and pre-activated meta I states. Retinal was labeled with 2 H at the C5, C9, or C13 methyl groups by total synthesis, and was used to regenerate the opsin apoprotein. Solid-state 2 H NMR spectra were acquired for aligned membranes in the lowtemperature lipid gel phase versus the tilt angle to the magnetic field. Data reduction assumed a static uniaxial distribution, and gave the retinylidene methyl bond orientations together with the alignment disorder (mosaic spread). The 2 H NMR structure of 11-cis-retinal in the dark state revealed torsional twisting of the polyene chain and the β-ionone ring. The distorted retinylidene ligand undergoes restricted motion, as evinced by order parameters of ≈ 0.9 for the rapidly spinning C-C 2 H 3 groups, with off-axial fluctuations of ≈ 15°. Retinal is accommodated within the rhodopsin binding pocket with a negative pre-twist about the C11=C12 double bond, which explains its rapid photochemistry and indicates the trajectory of the 11-cis to trans isomerization.For the cryotrapped meta I state, the 2 H NMR structure showed a reduction of the polyene strain, whereas the β-ionone ring maintained its torsional twisting. Strain energy and dynamics of retinal are interpreted with regard to substituent control of receptor activation. Steric hindrance between trans retinal and Trp 265 can trigger formation of the subsequent activated meta II state. Our results are pertinent to quantum and classical molecular mechanics simulations, and show how 2 H NMR can be applied to ligands bound to GPCRs in relation to their characteristic mechanisms of action.

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Section: Powder-type 2 H Nmr Spectra Of Retinal Bound To Rhodopsinmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Structural Analysis and Dynamics of Retinal Chromophore in Dark and Meta I States of Rhodopsin from 2H NMR of Aligned Membranes

Struts

Salgado

Tanaka

et al. 2007

Journal of Molecular Biology

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134

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“…The complete secondary structure of gram icidin and its dynamic properties in membranes have also been obtained using 2H and 15N NMR (6-9). In addition, the complete structure and orientation of deu terated retinal in bacteriorhodopsin at different states of its photocycle has been resolved (10), The average molecular and orientational order of lipids and peptides in liquid crystalline membranes could also be deter mined unambiguously in this way (11)(12)(13)(14).…”

mentioning

confidence: 99%

Macroscopic Orientation of Natural and Model Membranes for Structural Studies

Gröbner

Taylor

Williamson

et al. 1997

Analytical Biochemistry

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O ne a p p ro a ch for o b ta in in g h ig h -r eso lu tio n s tr u c tu ra l an d fu n ctio n a l in fo rm a tio n for b iom em b ran es an d th e ir p ro tein s is b y s ta tic so lid -sta te NMR o f o ri e n te d sy stem s. H ere, a g e n e r a l p ro ced u re to a lig n fu lly fu n c tio n a l b io lo g ica l m em b ra n es co n ta in in g large m em b ran e p ro tein s (Mr >30,000) is d escrib ed . T he m eth od , b a sed on th e iso p o te n tia l sp in -d ry u ltra ce n tr ifu g a tio n tech n iq u e , r e lie s on th e cen trifu g a tio n o f m em b ran e fra g m en ts on to a su p p o rt w ith sim u lta n e ous, or su b seq u en t, p a r tia l e v a p o r a tio n o f th e so lv e n t w h ic h a id s a lig n m en t. atu ral m em b ra n es w ith th e red c e ll a n io n ex ch a n g e tran sp ort p r o te in in ery th ro cy tes, b an d 3, an d th e n ico tin ic a c e ty lc h o lin e receptor. O 1997 Academic Press The elucidation of the structural and functional orga nization of biological membranes by various biophysi cal techniques is one of the important questions being addressed in structural biology. The complexity of the systems, however, their supramolecular structure, and their dynamic properties make direct studies particu larly difficult. Specifically, membrane proteins present extraordinary technical difficulties to the most com monly used methods in structural biology, such as crys tallography (1) and solution NMR spectroscopy (2). In 1 To whom correspondence should be addressed, Fax; 01865/275-234 or -259. E-mail: awatts@bioch.ox.ac.uk. 132recent years solid-state NMR spectroscopy (3, 4) on macroscopically oriented lipid bilayers has rapidly emerged as an alternative approach to elucidate struc tural and functional features of membrane-bound pep tides and proteins. In such aligned systems, lipids and proteins are arranged uniaxially around the mem brane, allowing normal orientation of the molecule backbone relative to the substratum. In combination with isotopic labeling (e.g., 2H, 13C, 15N) this NMR ap proach has successfully been used to determine the complete secondary structure of the M2 channel pep tide and fd coat protein (3), while the orientation of the antibiotic peptide magainin has been resolved in bilayers (5). The complete secondary structure of gram icidin and its dynamic properties in membranes have also been obtained using 2H and 15N NMR (6-9). In addition, the complete structure and orientation of deu terated retinal in bacteriorhodopsin at different states of its photocycle has been resolved (10), The average molecular and orientational order of lipids and peptides in liquid crystalline membranes could also be deter mined unambiguously in this way (11-14).Unfortunately, the generation of structural and ori entational information about membrane proteins has been limited mainly to peptides, since no general methods have been available for aligning native and reconstituted membranes containing larger integral membrane proteins in sufficient quality and quantity without affect...

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“…Additionally, we calculated the deuterium order parameters S CD profiles (Brown 1996) of acyl chains of lipids within the vicinity of Emodin and compared them with the profiles calculated from the simulations of pure-DMPC. Figure 9 shows the |S CD | profiles of the lipid sn-1 (Fig.…”

Section: Effect Of Emodin On the Lipid Bilayermentioning

confidence: 99%

Experimental and theoretical studies of emodin interacting with a lipid bilayer of DMPC

et al. 2017

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Emodin is one of the most abundant anthraquinone derivatives found in nature. It is the active principle of some traditional herbal medicines with known biological activities. In this work, we combined experimental and theoretical studies to reveal information about location, orientation, interaction and perturbing effects of Emodin on lipid bilayers, where we have taken into account the neutral form of the Emodin (EMH) and its anionic/deprotonated form (EM − ). Using both UV/Visible spectrophotometric techniques and molecular dynamics (MD) simulations, we showed that both EMH and EM − are located in a lipid membrane. Additionally, using MD simulations, we revealed that both forms of Emodin are very close to glycerol groups of the lipid molecules, with the EMH inserted more deeply into the bilayer and more disoriented relative to the normal of the membrane when compared with the EM − , which is more exposed to interfacial water. Analysis of several structural properties of acyl chains of the lipids in a hydrated pure DMPC bilayer and in the presence of Emodin revealed that both EMH and EM − affect the lipid bilayer, resulting in a remarkable disorder of the bilayer in the vicinity of the Emodin. However, the disorder caused by EMH is weaker than that caused by EM − . Our results suggest that these disorders caused by Emodin might lead to distinct effects on lipid bilayers including its disruption which are reported in the literature.

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Membrane Structure and Dynamics Studied with NMR Spectroscopy

Cited by 50 publications

References 126 publications

Structural Analysis and Dynamics of Retinal Chromophore in Dark and Meta I States of Rhodopsin from 2H NMR of Aligned Membranes

Structural Analysis and Dynamics of Retinal Chromophore in Dark and Meta I States of Rhodopsin from 2H NMR of Aligned Membranes

Macroscopic Orientation of Natural and Model Membranes for Structural Studies

Experimental and theoretical studies of emodin interacting with a lipid bilayer of DMPC

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