Nearest-Neighbor Recognition in Phospholipid Membranes

Davidson, Sharon M.K; Regen, Steven L.

doi:10.1021/cr960381s

Cited by 104 publications

(108 citation statements)

References 61 publications

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“…Although disulfide interchange reactions have been the subject of previous studies (79)(80)(81)(82)(83)(84)(85), there are no previous reports, to our knowledge, on the use of a disulfide coupled-folding approach to measure the energetics of reversible transmembrane peptide association in phospholipid bilayers. The development of experimental methods to study the folding in phospholipid environments holds great promise for providing detailed insights into the understanding of the membrane protein folding process.…”

Section: Discussionmentioning

confidence: 99%

Use of thiol-disulfide equilibria to measure the energetics of assembly of transmembrane helices in phospholipid bilayers

Cristian

Lear²,

DeGrado³

2003

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

142

185

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Despite significant efforts and promising progress, the understanding of membrane protein folding lags behind that of soluble proteins. Insights into the energetics of membrane protein folding have been gained from biophysical studies in membrane-mimicking environments (primarily detergent micelles). However, the development of techniques for studying the thermodynamics of folding in phospholipid bilayers remains a considerable challenge. We had previously used thiol-disulfide exchange to study the thermodynamics of association of transmembrane ␣-helices in detergent micelles; here, we extend this methodology to phospholipid bilayers. The system for this study is the homotetrameric M2 proton channel protein from the influenza A virus. Transmembrane peptides from this protein specifically self-assemble into tetramers that retain the ability to bind to the drug amantadine. Thiol-disulfide exchange under equilibrium conditions was used to quantitatively measure the thermodynamics of this folding interaction in phospholipid bilayers. The effects of phospholipid acyl chain length and cholesterol on the peptide association were investigated. The association of the helices strongly depends on the thickness of the bilayer and cholesterol levels present in the phospholipid bilayer. The most favorable folding occurred when there was a good match between the width of the apolar region of the bilayer and the hydrophobic length of the transmembrane helix. Physiologically relevant variations in the cholesterol level are sufficient to strongly influence the association. Evaluation of the energetics of peptide association in the presence and absence of cholesterol showed a significantly tighter association upon inclusion of cholesterol in the lipid bilayers.

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Section: Discussionmentioning

confidence: 99%

Use of thiol-disulfide equilibria to measure the energetics of assembly of transmembrane helices in phospholipid bilayers

Cristian

Lear²,

DeGrado³

2003

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

142

185

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“…[14] Such phase separation is similar to the formation of domains in mixed lipid monolayers and phospholipid membranes. [15,16] Scanning tunneling microscopy (STM) studies on gold nanoparticles have revealed pattern formation in mixed SAMs of alkane thiolates. [17,18] An X-ray study of bifunctional gold nanoparticles at the air-water interface suggests the formation of giant amphiphiles through segregation of hydrophobic and hydrophilic ligands.…”

Section: Introductionmentioning

confidence: 99%

Supramolecular Domains in Mixed Peptide Self‐Assembled Monolayers on Gold Nanoparticles

et al. 2008

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Self-organization in mixed self-assembled monolayers of small molecules provides a route towards nanoparticles with complex molecular structures. Inspired by structural biology, a strategy based on chemical cross-linking is introduced to probe proximity between functional peptides embedded in a mixed self-assembled monolayer at the surface of a nanoparticle. The physical basis of the proximity measurement is a transition from intramolecular to intermolecular cross-linking as the functional peptides get closer. Experimental investigations of a binary peptide self-assembled monolayer show that this transition happens at an extremely low molar ratio of the functional versus matrix peptide. Molecular dynamics simulations of the peptide self-assembled monolayer are used to calculate the volume explored by the reactive groups. Comparison of the experimental results with a probabilistic model demonstrates that the peptides are not randomly distributed at the surface of the nanoparticle, but rather self-organize into supramolecular domains.

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“…Thus, the DCLs are self -screening and the selected structures can be considered to be self -replicating. We proposed this possibility back in 2006 [18] , at which time the systems that came closest to showing such behavior were the disulfi de -bridged lipids developed by Regen et al [19] . It is gratifying to see that several systems have appeared since in which such internal templating is occurring.…”

Section: Self -Replication In DCL Smentioning

confidence: 99%