Designer short peptide surfactants stabilize G protein-coupled receptor bovine rhodopsin

Wang, Chao; Nagai, Yusuke; Reeves, Philip J.; Kiley, Patrick; Khorana, H G; Zhang, Shuguang

doi:10.1073/pnas.0607167103

Cited by 162 publications

(126 citation statements)

References 42 publications

Supporting

Mentioning

126

Contrasting

Order By: Relevance

“…Not only do peptides structurally resemble lipid molecules, but they also exhibit similar surfactant-like properties. Several earlier studies focused on their application as surfactants in membrane protein stabilization [18][19][20][21][22][23]. Their use as antimicrobial agents has also been considered [24,25].…”

Section: Introductionmentioning

confidence: 99%

Peptide self-assembly into lamellar phases and the formation of lipid-peptide nanostructures

et al. 2017

View full text Add to dashboard Cite

Lipids exhibit an extraordinary polymorphism in self-assembled mesophases, with lamellar phases as the most relevant biological representative. To mimic lipid lamellar phases with amphiphilic designer peptides, seven systematically varied short peptides were engineered. Indeed, four peptide candidates (V 4 D, V 4 WD, V 4 WD 2 , I 4 WD 2 ) readily self-assembled into lamellae in aqueous solution. Small-angle X-ray scattering (SAXS) patterns revealed ordered lamellar structures with a repeat distance of ~ 4-5 nm. Transmission electron microscopy (TEM) images confirmed the presence of stacked sheets. Two derivatives (V 3 D and V 4 D 2 ) remained as loose aggregates dispersed in solution; one peptide (L 4 WD 2 ) formed twisted tapes with internal lamellae and an antiparallel β-type monomer alignment. To understand the interaction of peptides with lipids, they were mixed with phosphatidylcholines. Low peptide concentrations (1.1 mM) induced the formation of a heterogeneous mixture of vesicular structures. Large multilamellar vesicles (MLV, d-spacing ~ 6.3 nm) coexisted with oligo-or unilamellar vesicles (~ 50 nm in diameter) and bicelle-like structures (~ 45 nm length, ~ 18 nm width). High peptide concentrations (11 mM) led to unilamellar vesicles (ULV, diameter ~ 260-280 nm) with a homogeneous mixing of lipids and peptides. SAXS revealed the temperature-dependent fine structure of these ULVs. At 25 °C the bilayer is in a fully interdigitated state (headgroup-to-headgroup distance d HH ~ 2.9 nm), whereas at 50 °C this interdigitation opens up (d HH ~ 3.6 nm). Our results highlight the versatility of self-assembled peptide superstructures. Subtle changes in the amino acid composition are key design elements in creating peptide-or lipidpeptide nanostructures with richness in morphology similar to that of naturally occurring lipids.

show abstract

Section: Introductionmentioning

confidence: 99%

Peptide self-assembly into lamellar phases and the formation of lipid-peptide nanostructures

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Lipopeptides, formed by linkage of fatty acid groups to peptides, have also been described for this purpose [61]. Short heptameric peptides (consisting of seven amino acids: a hydrophilic head, aspartic acid or lysine, and a hydrophobic tail with six consecutive alanine residues) are capable of efficiently extracting membrane proteins without additional incorporation of fatty acid or other lipophilic groups and can further maintain the activity of the extracted protein [62][63][64]. Rho has been stabilized towards thermal denaturation with this type of peptides, and based on this a model for peptide detergents-membrane proteins interaction is being proposed.…”

Section: New Solubilizing Agents For Membrane Proteinsmentioning

confidence: 99%

Stabilization of Membrane Proteins: the Case of G‐Protein‐Coupled Receptors

Reyes‐Alcaraz

Tzanov

Garriga

2008

Engineering in Life Sciences

View full text Add to dashboard Cite

G-protein-coupled receptors are integral membrane proteins which constitute the largest family of signal transduction molecules participating in the majority of normal physiological processes. G-protein-coupled receptors are responsible for the control of enzyme activity, ion channels and vesicle transport, and they respond to a wide variety of stimuli, like signals involved in sensory systems such as vision, taste and olfaction, but also to a diverse set of chemical signals such as lipids, hormones, neurotransmitters, amino acids, nucleotides, peptides and proteins. This family of receptors is being widely studied because of its potential use as pharmacological targets in drug development, and recently also for its potential use in the development of novel biosensors. G-protein-coupled receptors are specifically designed to fold and function in a lipid bilayer environment, where these membrane proteins are remarkably stable and achieve their optimal performance. The currently used technology for the purification of G-protein-coupled receptors consists in their extraction from the cell membrane and solubilization into detergent micelles. A common drawback of this strategy is that G-proteincoupled receptors solubilized in typical detergents show rather poor conformational stability, which may result in relatively rapid inactivation. The poor stability of detergent-solubilized samples renders many membrane proteins biochemically intractable. This precludes the determination of a high-resolution structure and imposes severe limitations for the development of applications. Thus, the enhancement of the stability of G-protein-coupled receptors is a major issue in order to facilitate structural determination and to unravel their potential in biotechnological applications. This work provides a brief overview of some current advances in the experimental methods for stabilizing G-protein-coupled receptors that can also be extended to other types of membrane proteins. Structure of G-protein-Coupled Receptors (GPCRs)The distinctive structural feature of GPCRs is the bundle of seven transmembrane (7TM) a-helices that constitutes a relevant signature in structural biology. This conformational architecture, and its functional implications, is central to pharmacology and therapeutics. Nearly 2000 GPCRs have been reported since bovine opsin was cloned in 1983 and the b-adrenergic receptor in 1986. They are classified into over 100 subfamilies as a function of their sequence homology, ligand structure and receptor function. Significant differences exist among the members of the GPCRs superfamily, in spite of the high degree of amino acid homology found among the members of a particular subfamily. The visual photoreceptor rhodopsin (Rho) was the first GPCR whose crystal structure was determined at high-resolution [1][2][3][4][5][6][7]. The natural abundance and availability of Rho has made of this protein the prototypical GPCR for structural studies. As a consequence, Rho is often selected as a model protein for biochemical and b...

show abstract

“…This category nanomaterial has been widely used in the area of nanoscience and biomedical engineering such as cell and tissue cultures, [1][2][3][4] biological surface engineering, [5][6] membrane protein stabilizations. 7 In recent years, these peptides have also been attracted great interest from scientists used for drug delivery system. [8][9][10] As we know, the self-assembly peptides lead to a unique amphiphilic structure because of numbers of hydrophobic and hydrophilic residues in the amino acid sequence.…”

Section: Introductionmentioning

confidence: 99%

Dynamic Research of a Potential Carrier for Hydrophobic Compound Model Pyrene Using Amphiphilic Peptide EYK

Wang¹,

Zhao²

2011

Bulletin of the Korean Chemical Society

View full text Add to dashboard Cite

In recent years, the study of self-assembly peptide used in drug delivery system has been attracted great interest from scientists. In the category are self-assembly peptides in the structure either with one hydrophobic surface and another hydrophilic or a hydrophobic head and a hydrophilic tail. Here, we focus on a novel designed peptide EYK with double amphiphilic surfaces, investigating on the capability of peptide as a carrier for hydrophobic compound model pyrene. The fluorescence data presented the dynamic process of the transfer, showing that the pyrene was in the crystalline form in peptide solution, and molecularly migrated from its peptide encapsulations into the membrane bilayers when the peptide-pyrene suspension was mixed with liposome vesicles. The results indicated that the peptide EYK could stabilize hydrophobic pyrene in aqueous solution and delivered it into EPC liposome as a potential carrier.

show abstract

Designer short peptide surfactants stabilize G protein-coupled receptor bovine rhodopsin

Cited by 162 publications

References 42 publications

Peptide self-assembly into lamellar phases and the formation of lipid-peptide nanostructures

Peptide self-assembly into lamellar phases and the formation of lipid-peptide nanostructures

Stabilization of Membrane Proteins: the Case of G‐Protein‐Coupled Receptors

Dynamic Research of a Potential Carrier for Hydrophobic Compound Model Pyrene Using Amphiphilic Peptide EYK

Contact Info

Product

Resources

About