Use of Synthetic Peptides for the Study of Membrane Protein Structure

Lear, J. D.; Wasserman, Zelda R.; DeGrado, William

doi:10.1007/978-1-4614-7515-6_15

Cited by 10 publications

(10 citation statements)

References 50 publications

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“…Thus the Alm molecule is not fully exposed to bulk water even though the Alm/surface simulation corresponds to a loose complex. This location of alamethicin relative to the bilayer contrasts with the models of, e.g., Wiener and White (1992), White (1994), Chung et al (1992), and Lear et al (1994), in which surface-bound helices are proposed to be closer to the hydrophobic core of the bilayer. These latter models may correspond to a tight complex.…”

Section: Resultscontrasting

confidence: 89%

“…The traditional view (Sansom, 1998) is that ␣-helix stabilization is due to partitioning of hydrophilic and hydrophobic side chains between the aqueous phase and the hydrophobic core of the bilayer, respectively. This requires the helix to be located deep in the interfacial region, as in the models of White (1994) and Lear et al (1994). Although this may be so in tighter peptide:bilayer complexes, it is not so in the loose complex described here.…”

Section: Discussionmentioning

confidence: 89%

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Surface Binding of Alamethicin Stabilizes its Helical Structure: Molecular Dynamics Simulations

Tieleman¹,

Berendsen²,

Sansom

1999

Biophysical Journal

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Alamethicin is an amphipathic alpha-helical peptide that forms ion channels. An early event in channel formation is believed to be the binding of alamethicin to the surface of a lipid bilayer. Molecular dynamics simulations are used to compare the structural and dynamic properties of alamethicin in water and alamethicin bound to the surface of a phosphatidylcholine bilayer. The bilayer surface simulation corresponded to a loosely bound alamethicin molecule that interacted with lipid headgroups but did not penetrate the hydrophobic core of the bilayer. Both simulations started with the peptide molecule in an alpha-helical conformation and lasted 2 ns. In water, the helix started to unfold after approximately 300 ps and by the end of the simulation only the N-terminal region of the peptide remained alpha-helical and the molecule had collapsed into a more compact form. At the surface of the bilayer, loss of helicity was restricted to the C-terminal third of the molecule and the rod-shaped structure of the peptide was retained. In the surface simulation about 10% of the peptide/water H-bonds were replaced by peptide/lipid H-bonds. These simulations suggest that some degree of stabilization of an amphipathic alpha-helix occurs at a bilayer surface even without interactions between hydrophobic side chains and the acyl chain core of the bilayer.

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Section: Resultscontrasting

confidence: 89%

Section: Discussionmentioning

confidence: 89%

Surface Binding of Alamethicin Stabilizes its Helical Structure: Molecular Dynamics Simulations

Tieleman¹,

Berendsen²,

Sansom

1999

Biophysical Journal

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“…Comparison with A/M2 and Other Proton Channels-It is interesting to compare the sequence of BM2 with that of A/M2 and LS2 (41)(42)(43), the latter being a four-helix bundle proton channel peptide that was designed from first principles and characterized before the sequence of BM2 had been elucidated (Sequences 3-5). The primary determinants of the pore in each of these peptides occur in a heptad repeat at pore-facing positions "a" and "d".…”

Section: Discussionmentioning

confidence: 99%

Identification of the Pore-lining Residues of the BM2 Ion Channel Protein of Influenza B Virus

Soto

Ohigashi

et al. 2008

Journal of Biological Chemistry

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The influenza B virus BM2 proton-selective ion channel is essential for virus uncoating, a process that occurs in the acidic environment of the endosome. The BM2 channel causes acidification of the interior of the virus particle, which results in dissociation of the viral membrane protein from the ribonucleoprotein core. The BM2 protein is similar to the A/M2 protein ion channel of influenza A virus (A/M2) in that it contains an HXXXW motif. Unlike the A/M2 protein, the BM2 protein is not inhibited by the antiviral drug amantadine. We used mutagenesis to ascertain the pore-lining residues of the BM2 ion channel. The specific activity (relative to wild type), reversal voltage, and susceptibility to modification by (2-aminoethyl)-methane thiosulfonate and N-ethylmaleimide of cysteine mutant proteins were measured in oocytes. . Based on these experimental data, a BM2 transmembrane domain model is proposed. The presence of polar residues in the pore is a probable explanation for the amantadine insensitivity of the BM2 protein and suggests that related but more polar compounds might serve as useful inhibitors of the protein.

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“…To explore a simple interfacial peptide we modelled and simulated LS3, a synthetic leucine/serine-containing peptide with sequence (LSSLLSL) 3 , which has been studied in detail by DeGrado and colleagues (Åkerfeldt et al, 1993;Dieckmann et al, 1999;Kienker et al, 1994;Lear et al, 1988Lear et al, , 1994Lear et al, , 1997. LS3 has been demonstrated to form anhelix which adopts an interfacial location parallel to the bilayer surface when monomeric.…”

Section: Peptidementioning

confidence: 99%

“…In earlier biophysical studies the focus was on naturally occurring anti-microbial peptides (Sansom, 1998). However, in recent years there has been considerable interest in two other classes of membrane peptide: (i) simple, 'designed' peptides (Choma et al, 2000;Cristian et al, 2005;Killian, 2003;Lear et al, 1988Lear et al, , 1994 which embody key principles of membrane protein organisation; and (ii) relatively small membrane proteins which are amenable to structural and spectroscopic studies. In particular, these systems have been studied via solid state NMR (Bechinger et al, 2004;Marassi et al, 2000;Marassi and Opella, 1998;Opella and Marassi, 2004;Sharpe et al, 2006;Zeri et al, 2003) and a number of other spectroscopic approaches using oriented bilayer systems (Kukol and Arkin, 1999) in order to determine the orientation of peptides and simple protein -helices relative to a lipid bilayer.…”

Section: Introductionmentioning

confidence: 98%