Dataset Information

Structural mimicry of the ?-helix in aqueous solution with an isoatomic ?/?/?-peptide backbone.

ABSTRACT: Artificial mimicry of ?-helices offers a basis for development of protein-protein interaction antagonists. Here we report a new type of unnatural peptidic backbone, containing ?-, ?-, and ?-amino acid residues in an ?????? repeat pattern, for this purpose. This unnatural hexad has the same number of backbone atoms as a heptad of ? residues. Two-dimensional NMR data clearly establish the formation of an ?-helix-like conformation in aqueous solution. The helix formed by our 12-mer ?/?/?-peptide is considerably more stable than the ?-helix formed by an analogous 14-mer ?-peptide, presumably because of the preorganized ? and ? residues employed.

SUBMITTER: Sawada T

PROVIDER: S-EPMC3141811 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

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Structural mimicry of the α-helix in aqueous solution with an isoatomic α/β/γ-peptide backbone.

Sawada Tomohisa T Gellman Samuel H SH

Journal of the American Chemical Society 20110426 19

Artificial mimicry of α-helices offers a basis for development of protein-protein interaction antagonists. Here we report a new type of unnatural peptidic backbone, containing α-, β-, and γ-amino acid residues in an αγααβα repeat pattern, for this purpose. This unnatural hexad has the same number of backbone atoms as a heptad of α residues. Two-dimensional NMR data clearly establish the formation of an α-helix-like conformation in aqueous solution. The helix formed by our 12-mer α/β/γ-peptide is ...[more]

PMID: 21520956

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Project description:Transmembrane domains of membrane proteins sometimes contain conserved charged or ionizable residues which may be essential for protein function and regulation. This work examines the molecular interactions of single Arg residues within a highly dynamic transmembrane peptide helix. To this end, we have modified the GW4,20ALP23 (acetyl-GGAW4(AL)7AW20AGA-amide) model peptide framework to incorporate Arg residues near the center of the peptide. Peptide helix formation, orientation and dynamics were analyzed by means of solid-state NMR spectroscopy to monitor specific 2H- or 15N-labeled residues. GW4,20ALP23 itself adopts a tilted orientation within lipid bilayer membranes. Nevertheless, the GW4,20ALP23 helix exhibits moderate to high dynamic averaging of NMR observables, such as 2H quadrupolar splittings or 15N-1H dipolar couplings, due to competition between the interfacial Trp residues on opposing helix faces. Here we examine how the helix dynamics are impacted by the introduction of a single Arg residue at position 12 or 14. Residue R14 restricts the helix to low dynamic averaging and a well-defined tilt that varies inversely with the lipid bilayer thickness. To compensate for the dominance of R14, the competing Trp residues cause partial unwinding of the helix at the C-terminal. By contrast, R12GW4,20ALP23 exits the DOPC bilayer to an interfacial surface-bound location. Interestingly, multiple orientations are exhibited by a single residue, Ala-9. Quadrupolar splittings generated by 2H-labeled residues A3, A5, A7, and A9 do not fit to the α-helical quadrupolar wave plot defined by residues A11, A13, A15, A17, A19, and A21. The discontinuity at residue A9 implicates a helical swivel distortion and an apparent 310-helix involving the N-terminal residues preceding A11. These molecular features suggest that, while arginine residues are prominent factors controlling transmembrane helix dynamics, the influence of interfacial tryptophan residues cannot be ignored.

Dataset Information

Structural mimicry of the ?-helix in aqueous solution with an isoatomic ?/?/?-peptide backbone.

Publications

Structural mimicry of the α-helix in aqueous solution with an isoatomic α/β/γ-peptide backbone.

Similar Datasets

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