Elastic properties of polyunsaturated phosphatidylethanolamines influence rhodopsin function

Teague, Walter E.; Soubias, Olivier; Petrache, Horia I.; Fuller, Nola; Hines, Kirk G.; Rand, R. P.; Gawrisch, Klaus

doi:10.1039/c2fd20095c

Cited by 57 publications

(51 citation statements)

References 38 publications

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“…20/80 DOTAP/DOPE), however, we observed a transition at alkaline pH, albeit with a non-zero end-point value indicating ~80% photoproduct was still in the activated MII state. This observation is not consistent with previous explanations due to negative membrane curvature on rhodopsin activation, [8a–g] and suggests an additional activation mechanism despite the unfavorable solvation energy cost at the protein-lipid-water interface.…”

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confidence: 99%

“…[8] Native RDM contain primarily lipids with phosphocholine (PC), phosphoethanolamine (PE), and phosphoserine (PS) headgroups with ~47% docosahexaenoic acid (22:6ω3) acyl chains. The mechanistic roles of these lipids are explained by (i) the flexible surface model (FSM), [8d, 8e] which proposes that the negative spontaneous curvature of PE lipids helps offset the solvation energy cost at the protein-lipid-water interface of activated MII; [8a–g] (ii) high [H + ] condensed on the membrane surface due to negatively charged PS lipids, which shifts the MI–MII equilibrium toward MII; [8i–l] and (iii) specific lipid-rhodopsin interactions, [8g, 8h] such as H-bonding between PE headgroups and newly exposed protein residues upon MII formation. [8g] We reveal here a completely new mode of rhodopsin activation in non-biological membranes that does not fit into any of these mechanisms (Figure 1).…”

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confidence: 99%

“…Given the favorable role of negative membrane spontaneous curvature on rhodopsin activation, [8a–g] we expect to observe a shift of the MI–MII equilibrium toward MII at increasing DOPE concentration. What we actually observed is completely on the contrary.…”

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A Usual G‐Protein‐Coupled Receptor in Unusual Membranes

et al. 2015

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G-protein-coupled receptors (GPCRs) are the largest family of membrane-bound receptors and constitute ~50% of all known drug targets. They offer great potential for membrane protein nanotechnologies. We report here a charge-interaction-directed reconstitution mechanism that induces spontaneous insertion of bovine rhodopsin, the eukaryotic GPCR, into both lipid- and polymer-based artificial membranes. We reveal a new allosteric mode of rhodopsin activation incurred by the non-biological membranes: the cationic membrane drives a transition from inactive MI to activated MII state in the absence of high [H+] or negative spontaneous curvature. We attribute this activation to the attractive charge interaction between the membrane surface and the deprotonated Glu134 residue of the rhodopsin-conserved ERY sequence motif that helps break the cytoplasmic “ionic lock”. This study unveils a novel design concept of non-biological membranes to reconstitute and harness GPCR functions in synthetic systems.

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A Usual G‐Protein‐Coupled Receptor in Unusual Membranes

et al. 2015

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“…Lipid-protein interactions (1) and the associated functions of biomembranes (2)(3)(4)(5)(6) are known to be significantly influenced by the composition (2,(7)(8)(9)(10)(11) and structure of the lipid bilayer (6,(11)(12)(13)(14)(15)(16). Recently, the importance of lipids in cellular membranes and tissues has made lipidomics (17) an emerging field in biomedical research.…”

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confidence: 99%

Area per Lipid and Cholesterol Interactions in Membranes from Separated Local-Field 13 C NMR Spectroscopy

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et al. 2014

Biophysical Journal

108

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Investigations of lipid membranes using NMR spectroscopy generally require isotopic labeling, often precluding structural studies of complex lipid systems. Solid-state (13)C magic-angle spinning NMR spectroscopy at natural isotopic abundance gives site-specific structural information that can aid in the characterization of complex biomembranes. Using the separated local-field experiment DROSS, we resolved (13)C-(1)H residual dipolar couplings that were interpreted with a statistical mean-torque model. Liquid-disordered and liquid-ordered phases were characterized according to membrane thickness and average cross-sectional area per lipid. Knowledge of such structural parameters is vital for molecular dynamics simulations, and provides information about the balance of forces in membrane lipid bilayers. Experiments were conducted with both phosphatidylcholine (dimyristoylphosphatidylcholine (DMPC) and palmitoyloleoylphosphatidylcholine (POPC)) and egg-yolk sphingomyelin (EYSM) lipids, and allowed us to extract segmental order parameters from the (13)C-(1)H residual dipolar couplings. Order parameters were used to calculate membrane structural quantities, including the area per lipid and bilayer thickness. Relative to POPC, EYSM is more ordered in the ld phase and experiences less structural perturbation upon adding 50% cholesterol to form the lo phase. The loss of configurational entropy is smaller for EYSM than for POPC, thus favoring its interaction with cholesterol in raftlike lipid systems. Our studies show that solid-state (13)C NMR spectroscopy is applicable to investigations of complex lipids and makes it possible to obtain structural parameters for biomembrane systems where isotope labeling may be prohibitive.

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“…(3) When lipid monolayers form a bilayer, i.e a flat sheet, their ability to bend is limited by the opposing lipid monolayer. Monolayers that have lowest energy when curved are now elastically deformed to be flat — they are under curvature elastic stress [29]. …”

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confidence: 99%

The role of membrane curvature elastic stress for function of rhodopsin-like G protein-coupled receptors

et al. 2014

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The human genome encodes about 800 different G protein-coupled receptors (GPCR). They are key molecules in signal transduction pathways that transmit signals of a variety of ligands such as hormones and neurotransmitters to the cell interior. Upon ligand binding, the receptors undergo structural transitions that either enhance or inhibit transmission of a specific signal to the cell interior. Here we discuss results which indicate that transmission of such signals can be strongly modulated by the composition of the lipid matrix into which GPCR are imbedded. Experimental results have been obtained on rhodopsin, a prototype GPCR whose structure and function is representative for the great majority of GPCR in humans. The data shed light on the importance of curvature elastic stress in the lipid domain for function of GPCR.

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Elastic properties of polyunsaturated phosphatidylethanolamines influence rhodopsin function

Cited by 57 publications

References 38 publications

A Usual G‐Protein‐Coupled Receptor in Unusual Membranes

A Usual G‐Protein‐Coupled Receptor in Unusual Membranes

Area per Lipid and Cholesterol Interactions in Membranes from Separated Local-Field 13 C NMR Spectroscopy

The role of membrane curvature elastic stress for function of rhodopsin-like G protein-coupled receptors

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