Hydrophobic interactions of peptides with membrane interfaces

White, Stephen H.; Wimley, William C.

doi:10.1016/s0304-4157(98)00021-5

Cited by 514 publications

(499 citation statements)

References 70 publications

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“…However, this type of approach, which simply uses a linear combination of the amino acids' hydrophilicity, was successfully used to predict antigenic sites within sequences of a broad range of antibodies and is thus mostly functional and empirical (26). Other hydrophobicity scales were used for comparison (49)(50)(51)(52)(53) and yielded qualitatively similar results, although not as linear as with the Hopp and Woods scaling (26).…”

Section: Calculation Ofmentioning

confidence: 85%

Role of molecular charge and hydrophilicity in regulating the kinetics of crystal growth

Elhadj

Yoreo

Hoyer

et al. 2006

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

249

323

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The composition of biologic molecules isolated from biominerals suggests that control of mineral growth is linked to biochemical features. Here, we define a systematic relationship between the ability of biomolecules in solution to promote the growth of calcite (CaCO 3) and their net negative molecular charge and hydrophilicity. The degree of enhancement depends on peptide composition, but not on peptide sequence. Data analysis shows that this rate enhancement arises from an increase in the kinetic coefficient. We interpret the mechanism of growth enhancement to be a catalytic process whereby biomolecules reduce the magnitude of the diffusive barrier, E k, by perturbations that displace water molecules. The result is a decrease in the energy barrier for attachment of solutes to the solid phase. This previously unrecognized relationship also rationalizes recently reported data showing acceleration of calcite growth rates over rates measured in the pure system by nanomolar levels of abalone nacre proteins. These findings show that the growth-modifying properties of small model peptides may be scaled up to analyze mineralization processes that are mediated by more complex proteins. We suggest that enhancement of calcite growth may now be estimated a priori from the composition of peptide sequences and the calculated values of hydrophilicity and net molecular charge. This insight may contribute to an improved understanding of diverse systems of biomineralization and design of new synthetic growth modulators.biomineral ͉ calcite ͉ proteins

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Section: Calculation Ofmentioning

confidence: 85%

Role of molecular charge and hydrophilicity in regulating the kinetics of crystal growth

Elhadj

Yoreo

Hoyer

et al. 2006

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

249

323

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“…Ala and Asp substitutions introduce residues with positive free energies of transfer from water to the bilayer interface (34 This unique mechanism of 4E10 epitope recognition (i.e., lipophilic residues at the periphery of the antigen binding site) may explain difficulties in eliciting neutralizing antibody responses to immunogens based on the 4E10 epitope. It has been previously proposed that these difficulties related to the suggested reactivity of 2F5 and 4E10 with cardiolipin, an endogenous phospholipid (25,43).…”

Section: Discussionmentioning

confidence: 99%

“…We began by introducing nonconservative mutations at residues in the apex of the CDRH3 loop that display favorable free energies of transfer from water to a bilayer interface (34). Explicitly, we substituted the most lipophilic residue in this region, tryptophan, with either alanine or aspartic acid (Table S1).…”

mentioning

confidence: 99%

Aromatic residues at the edge of the antibody combining site facilitate viral glycoprotein recognition through membrane interactions

Scherer

Leaman

Zwick

et al. 2010

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

109

118

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The broadly neutralizing anti-HIV antibody 4E10 recognizes an epitope very close to the virus membrane on the glycoprotein gp41. It was previously shown that epitope recognition improves in a membrane context and that 4E10 binds directly, albeit weakly, to lipids. Furthermore, a crystal structure of Fab 4E10 complexed to an epitope peptide revealed that the centrally placed, protruding H3 loop of the antibody heavy chain does not form peptide contacts. To investigate the hypothesis that the H3 loop apex might interact with the viral membrane, two Trp residues in this region were substituted separately or in combination with either Ala or Asp by site-directed mutagenesis. The resultant IgG variants exhibited similar affinities for an epitope peptide as WT 4E10 but lower apparent affinities for both viral membrane mimetic liposomes and Env(−) virus. Variants also exhibited lower apparent affinities for Env(+) virions and failed to significantly neutralize a number of 4E10-sensitive viruses. For the extremely sensitive HXB2 virus, variants did neutralize, but at 37-to >250-fold lower titers than WT 4E10, with Asp substitutions exerting a greater effect on neutralization potency than Ala substitutions. Because reductions in lipid binding reflect trends in neutralization potency, we conclude that Trp residues in the antibody H3 loop enable membrane proximal epitope recognition through favorable lipid interactions. The requirement for lipophilic residues such as Trp adjacent to the antigen binding site may explain difficulties in eliciting 4E10-like neutralizing antibody responses by immunization and helps define a unique motif for antibody recognition of membrane proximal antigens.4E10 | gp41 | HIV | neutralizing antibody | tryptophan

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“…The peptides Ac-18A-NH 2 , Ac-18A1-NH 2 , Ac-18A2-NH 2 , and Ac-18AY-NH 2 were a gift from V. Mishra and J. Segrest (University of Alabama at Birmingham, AL). The buffer (pH 7.0) used in all experiments was 10 mM HEPES, 50 mM KCl, 1 mM EDTA, and 3 mM NaN 3 .…”

Section: Methodsmentioning

confidence: 99%

“…Peptide model systems are increasingly being used for the elucidation of the principles of the insertion, folding, and structure of proteins and peptides in membranes (reviewed in [1][2][3][4]. A critical issue is the topology of peptides incorporated into lipid bilayers: does a particular model peptide equilibrate freely across the bilayer, form a stable transmembrane structure, or remain only on one surface?…”

mentioning

confidence: 99%

Determining the Membrane Topology of Peptides by Fluorescence Quenching

Wimley

White

1999

Biochemistry

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Determination of the topology of peptides in membranes is important for characterizing and understanding the interactions of peptides with membranes. We describe a method that uses fluorescence quenching arising from resonance energy transfer ("FRET") for determining the topology of the tryptophan residues of peptides partitioned into phospholipid bilayer vesicles. This is accomplished through the use of a novel lyso-phospholipid quencher (lysoMC), N-(7-hydroxyl-4-methylcoumarin-3-acetyl)-1-palmitoyl-2-hydroxy-sn-glycero-3-phosphoethanolamine. The design principle was to anchor the methylcoumarin quencher in the membrane interface by attaching it to the headgroup of lyso-phosphoethanolamine. We show that lysoMC can be incorporated readily into large unilamellar phospholipid vesicles to yield either symmetrically (both leaflets) or asymmetrically (outer leaflet only) labeled bilayers. LysoMC quenches the fluorescence of membrane-bound tryptophan by the Förster mechanism with an apparent R 0 that is comparable to the thickness of the hydrocarbon core of a lipid bilayer (∼25 Å). Consequently, the methylcoumarin acceptor predominantly quenches tryptophans that reside in the same monolayer as the probe. The topology of a peptide's tryptophan in membranes can be determined by comparing the quenching in symmetric and asymmetric lysoMC-labeled vesicles. Because it is essential to know that asymmetrically incorporated lysoMC remains so under all conditions, we also developed a second type of FRET experiment for assessing the rate of transbilayer diffusion (flip-flop) of lysoMC. Except in the presence of poreforming peptides, there was no measurable flip-flop of lysoMC, indicating that asymmetric distributions of quencher are stable. We used these methods to show that N-acetyl-tryptophan-octylamide and tryptophanoctylester rapidly equilibrate across phosphatidylcholine (POPC) and phosphatidylglycerol (POPG) bilayers, while four amphipathic model peptides remain exclusively on the outer monolayer. The topology of the amphipathic peptide melittin bound to POPC could not be determined because it induced rapid flip-flop of lysoMC. Interestingly, melittin did not induce lysoMC flip-flop in POPG vesicles and was found to remain stably on the external monolayer.Peptide model systems are increasingly being used for the elucidation of the principles of the insertion, folding, and structure of proteins and peptides in membranes (reviewed in 1-4). A critical issue is the topology of peptides incorporated into lipid bilayers: does a particular model peptide equilibrate freely across the bilayer, form a stable transmembrane structure, or remain only on one surface? The answer to this question clarifies the physicochemical state of a peptide in membranes and thus bears upon the biological activity of peptide model systems. The question is infrequently addressed, however, because there are only a few reliable methods for answering it. The methods fall into three classes. The most widely utilized methods include oriented diffra...

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Hydrophobic interactions of peptides with membrane interfaces

Cited by 514 publications

References 70 publications

Role of molecular charge and hydrophilicity in regulating the kinetics of crystal growth

Role of molecular charge and hydrophilicity in regulating the kinetics of crystal growth

Aromatic residues at the edge of the antibody combining site facilitate viral glycoprotein recognition through membrane interactions

Determining the Membrane Topology of Peptides by Fluorescence Quenching

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