Thermodynamic Analysis of Autonomous Parallel β-Sheet Formation in Water

Fisk, John D.; Schmitt, Margaret A.; Gellman, Samuel H.

doi:10.1021/ja060942p

Cited by 28 publications

(34 citation statements)

References 25 publications

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“…41 Figure 3 confirms that the chiral N-H stretch signal is observed for peptide 1 with parallel β-sheet with characteristic amide I bands (Figure 3). Two peaks at 1636 cm −1 and 1661 cm −1 are fitted into Eq.…”

Section: Orientationsupporting

confidence: 78%

Characterization of Parallel β-Sheets at Interfaces by Chiral Sum Frequency Generation Spectroscopy

Wang

Psciuk

et al. 2015

J. Phys. Chem. Lett.

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Characterization of protein secondary structures at interfaces is still challenging due to the limitations of surface-selective optical techniques. Here, we address the challenge of characterizing parallel β-sheets by combining chiral sum frequency generation (SFG) spectroscopy and computational modeling. We focus on human islet amyloid polypeptide aggregates and a de novo designed short polypeptide on at lipid/water and air/glass interfaces. We find that parallel β-sheets adopt distinct orientations at various interfaces and exhibit characteristic chiroptical responses in the amide I, and N-H stretch regions. Theoretical analysis indicates that the characteristic chiroptical responses provide valuable information on the parallel β-sheet symmetry, orientation and vibrational couplings at interfaces.

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Section: Orientationsupporting

confidence: 78%

Characterization of Parallel β-Sheets at Interfaces by Chiral Sum Frequency Generation Spectroscopy

Wang

Psciuk

et al. 2015

J. Phys. Chem. Lett.

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“…The dC a H value for each indicator residue in a member of the series was used along with the dC a H value for the analogous residue in P-L, representing the fully unfolded state, and the dC a H value for the analogous residue in P-cyc, representing the fully folded state (see Figure S7 in the Supporting Information), to estimate parallel-b-sheet population based on a two-state assumption (folded vs. unfolded). [25,31] The free energy for folding (DG f ) was calculated from the NMR-derived b-sheet population. Members of the P(T!V) n series were compared in terms of the DDG f value, calculated relative to parent peptide P (Figure 3 b).…”

Section: Methodsmentioning

confidence: 99%

Impact of Strand Length on the Stability of Parallel‐β‐Sheet Secondary Structure

et al. 2011

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The thousands of tertiary structural motifs known among natural proteins are built up from a handful of regular secondary structures, mostly a helices and b sheets, which are linked by b turns and larger loops. Sequence-stability relationships for a helices [1][2][3] and for antiparallel b sheets [4][5][6][7] have been widely explored using autonomously folding peptides, an experimental approach that eliminates the potentially confounding influence of a specific tertiary context. In contrast, a minimal parallel b sheet cannot readily be generated within a conventional peptide because the N terminus of one strand is necessarily distant from the C terminus of a neighboring strand. A continuous peptide design for a parallel b sheet would require a long interstrand loop, introducing significant tertiary packing effects or an entropic penalty for folding, either of which would compromise the analysis. Thus, novel strategies are required to elucidate the factors that govern parallel-b-sheet stability. [8,9] Herein we use recently developed tools, including short nonpeptidic units for connecting peptide strands through their C termini, [10,11] to explore a fundamental question: does parallel-b-sheet secondary structure become more stable as the strands grow longer? The a helix is well known to be stabilized by increasing length.[12-15] a-Helix initiation (ordering of the first four residues, to enable formation of the first intrahelical H-bond) entails a large entropic cost, which can be offset by a small but favorable energetic gain from propagation (incorporation of individual residues into a preexisting helix). [16][17][18] The longer the a helix, the larger the net thermodynamic benefit from propagation, if the residues have a favorable helix propensity. In contrast, antiparallel-bsheet secondary structure appears to be subject to an intrinsic limit on strand length. [19] The relationship between strand length and parallel-b-sheet stability has not previously been addressed. This gap in experimentation may underlie the relatively limited theoretical treatment of b-sheet formation, [20][21][22] especially for parallel b sheets, [20] which stands in contrast to the extensive theoretical analysis of a-helical folding. [16][17][18] Herein, we show that parallel b sheets becomes steadily more stable as the strands are lengthened, if the added residues have a high b-sheet propensity.Our experimental design is outlined in Figure 1 a. A diamine segment containing d-proline is used to link two strand-forming peptide segments through their C termini. [10,23] This linker promotes but does not strictly enforce bsheet interactions between attached strands in aqueous solution. The extent of b-sheet formation is monitored by NMR spectroscopy [24,25] by measuring a-proton chemical shifts (dC a H) at "indicator" residues (black dots) within the core segment (black) as the strands are extended incrementally (blue). The indicator residues are insulated from the extension segments by an intervening residue; therefore, changes in dC a H...

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“…However, if the small aromatic amino acid is instead in the C-terminal position (10,13,19) then the upfield shift is chemically significant for CSI (*0.10 ppm). It is interesting to note that the upfield shifts are not additive, and when two small amino acids are incorporated into a model peptide (8,11,17,20,21) the upfield shift is still chemically significant for CSI, but the magnitude does not appreciably increase beyond that of a single small aromatic amino acid in the C-terminal position. (All histidine containing peptides were studied at pH 2.8-3.0.…”

Section: Neighboring Amino Acidsmentioning

confidence: 99%

“…[6][7][8] CSI is of particular importance for those designing peptides that form discrete and stable -hairpins, because with relatively straightforward 1D and 2D NMR studies, information about protein secondary structure can be quickly obtained. [9][10][11][12][13][14][15] While CSI also applies to amide proton (HN), - 13 C, carbonyl 13 C, and amide 15 NH chemical shifts, the current study focuses on -proton chemical shifts. 8,16,17 In CSI the -proton of a particular amino acid in the protein is referenced to the random coil value for that amino acid.…”

Section: Introductionmentioning

confidence: 99%

“…19,[23][24][25] Groups studying -hairpin structure have resorted to synthesizing at least two peptides for each hairpin studied, one with -hairpin structure and a control peptide of similar sequence with no hairpin structure, to account for the shift effects of neighboring amino acids. [9][10][11][12][13][14] In the current study it is our goal to add to the collective knowledge of chemical shift effects and correction factors by systematically studying the effect of solution environments (pH, urea) and molecular environments (peptide length, free vs. capped termini, and neighboring amino acids) on -proton chemical shifts. It is important for the CSI community to understand not only the range of variables that cause significant chemical shift effects, but also the magnitude of the shift effects.…”

Section: Introductionmentioning

confidence: 99%

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Effect of pH, urea, peptide length, and neighboring amino acids on alanine α‐proton random coil chemical shifts

et al. 2006

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Accurate random coil α‐proton chemical shift values are essential for precise protein structure analysis using chemical shift index (CSI) calculations. The current study determines the chemical shift effects of pH, urea, peptide length and neighboring amino acids on the α‐proton of Ala using model peptides of the general sequence GnXaaAYaaGn, where Xaa and Yaa are Leu, Val, Phe, Tyr, His, Trp or Pro, and n = 1–3. Changes in pH (2–6), urea (0–1M), and peptide length (n = 1–3) had no effect on Ala α‐proton chemical shifts. Denaturing concentrations of urea (8M) caused significant downfield shifts (0.10 ± 0.01 ppm) relative to an external DSS reference. Neighboring aliphatic residues (Leu, Val) had no effect, whereas aromatic amino acids (Phe, Tyr, His and Trp) and Pro caused significant shifts in the alanine α‐proton, with the extent of the shifts dependent on the nature and position of the amino acid. Smaller aromatic residues (Phe, Tyr, His) caused larger shift effects when present in the C‐terminal position (∼0.10 vs. 0.05 ppm N‐terminal), and the larger aromatic tryptophan caused greater effects in the N‐terminal position (0.15 ppm vs. 0.10 C‐terminal). Proline affected both significant upfield (0.06 ppm, N‐terminal) and downfield (0.25 ppm, C‐terminal) chemical shifts. These new Ala correction factors detail the magnitude and range of variation in environmental chemical shift effects, in addition to providing insight into the molecular level interactions that govern protein folding. © 2006 Wiley Periodicals, Inc. Biopolymers 85: 72–80, 2007.This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com

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Thermodynamic Analysis of Autonomous Parallel β-Sheet Formation in Water

Cited by 28 publications

References 25 publications

Characterization of Parallel β-Sheets at Interfaces by Chiral Sum Frequency Generation Spectroscopy

Characterization of Parallel β-Sheets at Interfaces by Chiral Sum Frequency Generation Spectroscopy

Impact of Strand Length on the Stability of Parallel‐β‐Sheet Secondary Structure

Effect of pH, urea, peptide length, and neighboring amino acids on alanine α‐proton random coil chemical shifts

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