Lipid-protein interactions mediate the photochemical function of rhodopsin

Wiedmann, Timothy S.; Pates, Robert D.; Beach, J. M.; Salmon, Amir; Brown, Michael F.

doi:10.1021/bi00417a041

Cited by 156 publications

(218 citation statements)

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“…The resulting signals correspond to the 'a' and 'b' waves of the electroretinogram. Membrane fatty acid composition affects the ability of photons to transform rhodopsin to the activated state (Weidmann et al 1988;Mitchell et al 1992). The rhodopsin activation in response to light involves a transformation of the metarhodopsin I form to the metarhodopsin II form.…”

Section: Essential Fatty Acid Supply Affects Lipid Membrane Structurementioning

confidence: 99%

Essential fatty acids in early life: structural and functional role

2000

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Essential fatty acids (EFA) are structural components of all tissues and are indispensable for cell membrane synthesis; the brain, retina and other neural tissues are particularly rich in long-chain polyunsaturated fatty acids (LCPUFA). These fatty acids serve as specific precursors for eicosanoids that regulate numerous cell and organ functions. Results from animal and recent human studies support the essential nature of n-3 EFA in addition to the well-established role of n-6 EFA for human subjects, particularly in early life. The most significant effects relate to neural development and maturation of sensory systems. Recent studies using stable-isotope-labelled tracers demonstrate that even preterm infants are able to form arachidonic acid (AA) and docosahexaenoic acid (DHA), but that synthesis is extremely low. Intracellular fatty acids or their metabolites regulate transcriptional activation of gene expression during adipocyte differentiation, and retinal and nervous system development. Regulation of gene expression by LCPUFA occurs at the transcriptional level and is mediated by nuclear transcription factors activated by fatty acids. These nuclear receptors are part of the steroid hormone receptor family. Two types of polyunsaturated fatty acid responsive transcription factors have been characterized, the peroxisome proliferator-activated receptor (PPAR) and the hepatic nuclear factor 4α. DHA also has significant effects on photoreceptor membranes involved in the signal transduction process, rhodopsin activation, and rod and cone development. Comprehensive clinical studies have shown that dietary supplementation with marine oil or single-cell oils, sources of LCPUFA, results in increased blood levels of DHA and AA, as well as an associated improvement in visual function in formula-fed premature infants to match that of human milk-fed infant. Recent clinical trials convincingly support LCPUFA supplementation of preterm infant formulations and possibly term formula to mimic human milk composition.

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Section: Essential Fatty Acid Supply Affects Lipid Membrane Structurementioning

confidence: 99%

Essential fatty acids in early life: structural and functional role

2000

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“…For MAS NMR spectroscopy experiments, the labeled rhodopsin was concentrated and reconstituted into dioleolyl phosphatidylcholine vesicles by octyl-␤-D-glucoside dialysis in the presence of the phospholipid at a 300:1 molar ratio of lipid to protein (24)(25)(26). The extent of reconstitution was determined by UV͞Vis spectroscopy on samples resolubilized with detergent.…”

Section: Large-scale Expression Of Isotope-labeled Rhodopsinmentioning

confidence: 99%

Magic angle spinning NMR of the protonated retinylidene Schiff base nitrogen in rhodopsin: Expression of ¹⁵ N-lysine- and ¹³ C-glycine-labeled opsin in a stable cell line

Eilers

Reeves²,

Ying³

et al. 1999

Proc. Natl. Acad. Sci. U.S.A.

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The apoprotein corresponding to the mammalian photoreceptor rhodopsin has been expressed by using suspension cultures of HEK293S cells in defined media that contained 6-15 N-lysine and 2-13 C-glycine. Typical yields were 1.5-1.8 mg͞liter. Incorporation of 6-15 N-lysine was quantitative, whereas that of 2-13 C-glycine was about 60%. The rhodopsin pigment formed by binding of 11-cis retinal was spectrally indistinguishable from native bovine rhodopsin. Magic angle spinning (MAS) NMR spectra of labeled rhodopsin were obtained after its incorporation into liposomes. The 15 N resonance corresponding to the protonated retinylidene Schiff base nitrogen was observed at 156.8 ppm in the MAS spectrum of 6-15 N-lysine-labeled rhodopsin. This chemical shift corresponds to an effective Schiff base-counterion distance of greater than 4 Å, consistent with structural water in the binding site hydrogen bonded with the Schiff base nitrogen and the Glu-113 counterion. The present study demonstrates that structural studies of rhodopsin and other G protein-coupled receptors by using MAS NMR are feasible.Considerable progress has been made in recent years in understanding structure-function relationships in rhodopsin, the mammalian photoreceptor, and other members of the G protein-coupled receptor family (1-3). These receptors share a common structural motif consisting of seven transmembrane helices ( Fig. 1). Electron diffraction measurements of twodimensional rhodopsin crystals have revealed the spatial arrangement of the seven transmembrane helices (4, 5), whereas a combination of systematic cysteine replacements in the cytoplasmic domain of the receptor followed by spin labeling and EPR measurements has begun to show the nature of the movements in the transmembrane helices that are involved in receptor activation (6-8). An essential feature of the activation mechanism that emerges from these studies is that structural changes in the transmembrane domain are tightly coupled to the conformations of the cytoplasmic and intradiscal (extracellular) loops of the protein.In rhodopsin, receptor activation is controlled by the retinylidene chromophore. The 11-cis isomer of retinal is covalently attached as a protonated Schiff base (PSB) in the interior of the transmembrane domain. Photochemical isomerization of the retinal breaks helix-helix interactions, which, in the dark, lock rhodopsin in the inactive conformation. The idea that receptor-specific helix-helix interactions are involved in activation has arisen in studies on a number of G proteincoupled receptors (GPCRs) (2). Unfortunately, the lack of a high-resolution structure of rhodopsin, or of any other GPCR, has presented a formidable problem for establishing how the transmembrane helices pack and how structural changes in the transmembrane helices are coupled to ligand binding, retinal isomerization, or motion in the other domains of the receptor.Magic angle spinning (MAS) NMR spectroscopy has been increasingly applied to investigate membrane proteins over the past 10 yea...

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“…In earlier reconstitution experiments with bovine rhodopsin it was established that the equilibrium concentration of Meta-II rhodopsin increased with the concentration of DHA hydrocarbon chains in the lipid matrix (5)(6)(7). Also the headgroups of phospholipids had a significant effect on Meta-II formation (5,7) and activation of G t (8,9).…”

mentioning

confidence: 98%

“…Also the headgroups of phospholipids had a significant effect on Meta-II formation (5,7) and activation of G t (8,9). It was observed that phosphatidylethanolamines (PE) and the negatively charged phosphatidylserines (PS) increased the amount of Meta-II.…”

mentioning

confidence: 99%

Evidence for Specificity in Lipid-Rhodopsin Interactions

Soubias

Teague

Gawrisch

2006

Journal of Biological Chemistry

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The interaction of bovine rhodopsin with poly-and monounsaturated lipids was studied by 1 H MAS NMR with magnetization transfer from rhodopsin to lipid. Experiments were conducted on bovine rod outer segment (ROS) disks and on recombinant membranes containing lipids with polyunsaturated, docosahexaenoyl (DHA) chains. Poly-and monounsaturated lipids interact specifically with different sites on the rhodopsin surface. Rates of magnetization transfer from protein to DHA are lipid headgroup-dependent and increased in the sequence PC < PS < PE. Boundary lipids are in fast exchange with the lipid matrix on a time scale of milliseconds or shorter. All rhodopsin photointermediates transferred magnetization preferentially to DHA-containing lipids, but highest rates were observed for Meta-III rhodopsin. The experiments show clearly that the surface of rhodopsin has sites for specific interaction with lipids. Current theories of lipid-protein interaction do not account for such surface heterogeneity.Rhodopsin is the light receptor responsible for dim light vision in the rod photoreceptor cells of vertebrates. A large body of research demonstrated that efficiency of the rhodopsindependent steps of the visual process is exquisitely sensitive to membrane lipid composition, in particular to the content of -3 polyunsaturates (1-3). Retinal membranes of mammals, similar to synaptosomal membranes in brain, contain up to 50 mol % of docosahexaenoic acid (DHA, 2 22:6n3), a polyunsaturated fatty acid with 22 carbon atoms and six double bonds that are evenly distributed over the length of the chain (4).In earlier reconstitution experiments with bovine rhodopsin it was established that the equilibrium concentration of Meta-II rhodopsin increased with the concentration of DHA hydrocarbon chains in the lipid matrix (5-7). Also the headgroups of phospholipids had a significant effect on Meta-II formation (5, 7) and activation of G t (8, 9). It was observed that phosphatidylethanolamines (PE) and the negatively charged phosphatidylserines (PS) increased the amount of Meta-II.The influence of PS on the equilibrium was assigned to changes of the membrane electric surface potential (7). In contrast, the sensitivity of membranes to PE content correlated with an alteration of membrane curvature elasticity (10) as proposed for other membrane proteins by Navarro et al. (11), Jensen and Schutzbach (12), Gruner (13), Lindblom and coworkers (14), and Cantor (15). Litman and co-workers (6, 16) found a correlation between mobility and orientation of the fluorescence probe DPH in lipid bilayers, summarized as a membrane free volume parameter, and Meta-II formation. Furthermore, they observed a preference of rhodopsin to locate in domains rich in di-22:6n3-PC that formed in di-16:0-PC/ di-22:6-PC/cholesterol mixtures. Mouritsen proposed a link between hydrophobic thickness of lipid bilayers and activity of membrane proteins (18). Brown and co-workers (10) suggested that Meta-II has a greater hydrophobic thickness than Meta-I, and that the lipid bilayer...

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Lipid-protein interactions mediate the photochemical function of rhodopsin

Cited by 156 publications

References 42 publications

Essential fatty acids in early life: structural and functional role

Essential fatty acids in early life: structural and functional role

Magic angle spinning NMR of the protonated retinylidene Schiff base nitrogen in rhodopsin: Expression of ¹⁵ N-lysine- and ¹³ C-glycine-labeled opsin in a stable cell line

Evidence for Specificity in Lipid-Rhodopsin Interactions

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Lipid-protein interactions mediate the photochemical function of rhodopsin

Cited by 156 publications

References 42 publications

Essential fatty acids in early life: structural and functional role

Essential fatty acids in early life: structural and functional role

Magic angle spinning NMR of the protonated retinylidene Schiff base nitrogen in rhodopsin: Expression of 15 N-lysine- and 13 C-glycine-labeled opsin in a stable cell line

Evidence for Specificity in Lipid-Rhodopsin Interactions

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Magic angle spinning NMR of the protonated retinylidene Schiff base nitrogen in rhodopsin: Expression of ¹⁵ N-lysine- and ¹³ C-glycine-labeled opsin in a stable cell line