The Magic of Bicelles Lights Up Membrane Protein Structure

Dürr, U.; Gildenberg, Melissa; Ramamoorthy, Ayyalusamy

doi:10.1021/cr300061w

Cited by 314 publications

(272 citation statements)

References 318 publications

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“…Here we utilized the POPC/CHAPS bicelle system to reconstitute Rho. Various bicelle systems have been shown to retain the structural and functional integrity of membrane proteins (18). Previously, we have shown that the binding product between 11CR and photobleached Alexa488-labeled Rho in the bicelle system could be repeatedly photoactivated, demonstrating the regeneration of mature pigment (19).…”

Section: Discussionmentioning

confidence: 88%

Measurement of Slow Spontaneous Release of 11-cis-Retinal from Rhodopsin

Tian

Sakmar

Huber

2017

Biophysical Journal

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The vertebrate visual photoreceptor rhodopsin (Rho) is a unique G protein-coupled receptor as it utilizes a covalently tethered inverse agonist (11-cis-retinal) as the native ligand. Previously, electrophysiological studies showed that ligand binding of 11-cis-retinal in dark-adapted Rho was essentially irreversible with a half-life estimated to be 420 years, until after thermal isomerization to all-trans-retinal, which then slowly dissociates. This long lifetime of 11-cis-retinal binding was considered to be physiologically important for minimizing background signal (dark noise) of the visual system. However, in vitro biochemical studies on the thermal stability of Rho showed that Rho decays with a half-life on the order of days. In this study, we resolve the discrepancy by measuring the chromophore exchange rate of the bound 11-cis-retinal chromophore with free 9-cis-retinal from Rho in an in vitro phospholipid/detergent bicelle system. We conclude that the thermal decay of Rho primarily proceeds through spontaneous breaking of the covalent linkage between opsin and 11-cis-retinal, which was overlooked in the electrophysiological recording. We estimate that this slow spontaneous release of 11-cis-retinal from Rho should result in 10 4 to 10 5 free opsin molecules in a dark-adapted rod cell-a number that is three orders of magnitude higher than previously expected. We also discuss the physiological implications of these findings on the basal activity of opsins and the associated dark noise in the visual system.

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Section: Discussionmentioning

confidence: 88%

Measurement of Slow Spontaneous Release of 11-cis-Retinal from Rhodopsin

Tian

Sakmar

Huber

2017

Biophysical Journal

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“…52,53 The resulting structures (often referred to as bicelles) are stable and can be used as membrane model systems. 23 Conceptually, the stabilizing short-chain lipids are similar to linactant lipids that reduce the line tension at the interface between different lipid domains, e.g., between liquid-ordered and liquid-disordered domains in biological membranes. 54 This approach appears more suitable to study model systems because the perturbation is localized in a narrow region at the patch periphery and does not significantly perturb the strength of lipid-lipid and lipid-protein interactions.…”

Section: B Numerical Calculations and Results Of The Simplified Modelmentioning

confidence: 99%

“…1. Borrowing an effect commonly observed in nature, 23 the tuning of the edge energy in MD simulations has been achieved by adding short-chain phospholipids to the strongly curved bilayer edge. While the evolution towards a closed vesicle reduces the length of the water-exposed rim, the membrane bending upon vesiculation is energetically costly.…”

Section: B Doped Flat Bilayers With Free Boundariesmentioning

confidence: 99%

Peptide-induced membrane curvature in edge-stabilized open bilayers: A theoretical and molecular dynamics study

Pannuzzo

Raudino

Böckmann

2014

The Journal of Chemical Physics

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Peptide-or protein-induced curvatures of lipid membranes may be studied in molecular dynamics (MD) simulations. In these, membranes are usually modeled as infinitely extended bilayers by using periodic boundary conditions. However, the enforced periodicity results in an underestimation of the bending power of peptides, unless the patch size is much larger than the induced curvature radii. In this letter, we propose a novel approach to evaluate the bending power of a given distribution and/or density of peptides based on the use of flat open-edged lipid patches. To ensure long-lived metastable structures, the patch rim is stabilized in MD simulations by a local enrichment with short-chain lipids. By combining the theory of continuum elastic media with MD simulations, we prove that open-edged patches evolve from a planar state to a closed vesicle, with a transition rate that strongly depends on the concentration of lipid soluble peptides. For close-to-critical values for the patch size and edge energy, the response to even small changes in peptide concentration adopts a transition-like behavior (buckling instability). The usage of open-edged membrane patches amplifies the bending power of peptides, thereby enabling the analysis of the structural properties of membrane-peptide systems. We applied the presented method to investigate the curvature induced by aggregating β -amyloid peptides, unraveling a strong sensitivity of membrane deformation to the peptide concentration.

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“…Bicelles are a fabulous category of lipid assemblies that have been extensively employed as membrane models for structural characterization and biophysicochemical study of membrane‐bound proteins 46. They consist of two types of phospholipids, which are long‐chain phospholipids that make up a planar region, and either detergent or short‐chain phospholipids that compose flanking rims.…”

Section: Bihbsmentioning

confidence: 99%

Advancing the Pharmaceutical Potential of Bioinorganic Hybrid Lipid‐Based Assemblies

Wang

et al. 2018

Advanced Science

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Bioinspired lipid assemblies that mimic the elaborate architecture of natural membranes have fascinated researchers for a long time. These lipid assemblies have gone from being just an imperative platform for biophysical research to a pharmaceutical delivery system for biomedical applications. Despite success, these organized nanosystems are often subject to the mechanical instability and limited theranostic capability without adding any inconvenient modifications. To reach their advanced pharmaceutical potential, various bioinorganic hybrid lipid‐based assembles, which provide new opportunities to synergistically complement and improve therapeutic/diagnostic potential of existing lipid‐based nanomedicine with distinct mechanisms containing inorganic embedded surfactants, have recently been developed.

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The Magic of Bicelles Lights Up Membrane Protein Structure

Cited by 314 publications

References 318 publications

Measurement of Slow Spontaneous Release of 11-cis-Retinal from Rhodopsin

Measurement of Slow Spontaneous Release of 11-cis-Retinal from Rhodopsin

Peptide-induced membrane curvature in edge-stabilized open bilayers: A theoretical and molecular dynamics study

Advancing the Pharmaceutical Potential of Bioinorganic Hybrid Lipid‐Based Assemblies

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