The Structure of Unfolded Peptides and Proteins Explored by Vibrational Spectroscopy

Schweitzer‐Stenner, Reinhard; Measey, Thomas J.; Hagarman, Andrew; Dragomir, Isabelle

doi:10.1002/9780470602614.ch7

Cited by 10 publications

(18 citation statements)

References 128 publications

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“…3 Other parameter sets reported by the Bax-group yield very similar Karplus curves. 4,5 For reasons detailed below we also used Karplus parameters which were obtained with DFT calculations for alanine-based peptides for 3 J(H α ,C'). 6 For 1 J(N,C α ), we use the parameters reported by Wirmer and Schwalbe.…”

Section: J-coupling Constants and Karplus Parametersmentioning

confidence: 99%

“…Although IDPs do not have a single well-defined native structure, they are involved in many life-sustaining biological processes. [1][2][3][4] This disconnect between structure and function has challenged the now outdated central dogma of protein biophysics that a welldefined protein structure is necessary for function. Early attempts to characterize IDPs in structural terms treated them as unfolded proteins and categorized their conformational ensembles in terms of two states, i.e.…”

Section: Introductionmentioning

confidence: 99%

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Short peptides as predictors for the structure of polyarginine sequences in disordered proteins

Milorey

Schweitzer‐Stenner

Andrews

et al. 2021

Biophysical Journal

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Intrinsically disordered proteins are rich in charged and deficient in hydrophobic residues. High net charges of disordered protein segments favor statistical coil ensembles which are more extended than a self-avoiding random coil. It is unclear whether the chain extension solely reflects the avoidance of non-local interactions or also local nearest neighbor interactions provide significant contributions. The relevance of nearest neighbor interactions, which are neglected in random coil models, has been emphasized in the literature, but only sporadically considered in molecular modellings of disordered proteins and peptides. We determined the Ramachandran distributions of protonated arginine in GRRG and GRRRG peptides. Our results reveal the contribution of nearest neighbor interactions to the extended conformations reported for a variety of poly-arginine protein segments.

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Section: J-coupling Constants and Karplus Parametersmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Short peptides as predictors for the structure of polyarginine sequences in disordered proteins

Milorey

Schweitzer‐Stenner

Andrews

et al. 2021

Biophysical Journal

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“…19 For lysine in alaninebased peptides, we obtained mixtures of pPII, β-strand, and even right-handed helical conformations. 32 This discrepancy between reported distributions of isolated lysine in alanine/ glycine-based host peptides and lysine in polylysine might be indicative of substantial nearest neighbor interactions between adjacent lysine or glutamic acid residues. A clarification of this issue is of general relevance owing to the frequent occurrence of lysine in functionally relevant disordered motifs and loops.…”

Section: ■ Introductionmentioning

confidence: 98%

“…It is now well-established that the unfolded state of peptides and proteins is not as conformationally random as suggested by the random coil model, − which basically assumes that each amino acid besides proline equally populates a rather broad region in the upper left quadrant of the Ramachandran plot (−180° ≤ Φ ≤ −50° and 90° ≤ ψ ≤ 180°, region I), a slightly less extended trough located below the interface between upper and lower left quadrants (−180° ≤ Φ ≤ −30° and −80° ≤ ψ ≤ 30°; region II), and a more restricted one in the upper right quadrant (60° ≤ Φ ≤ 90° and 0° ≤ ψ ≤ 60°, region III). − Numerous experimental data as well as results obtained from the analysis of truncated coil libraries suggest that most amino acid residues have a strong preference for region I, whereas region II is much less populated than predicted by the random coil model. ,− However, some amino acid residues, such as serine, cysteine, threonine, asparagine, and particularly aspartic acid, the side chains of which all can either donate or accept hydrogen bonding, do not belong in this category, owing to their relatively strong preference for structures that appear in various turns or can themselves be considered as turns. , Conformational analyses of short peptides further indicate that region I contains at least two distinguishable subregions associated with polyproline II (pPII) and β-strand conformations (−100° ≤ Φ ≤ −60°, 130° ≤ ψ ≤ 180° and −180° ≤ Φ ≤ −100°, 90° ≤ ψ ≤ 180°, respectively). ,,,,− Different amino acid residues have been shown to exhibit different populations of pPII and β-strand. Alanine, for instance, has a very high propensity for pPII, whereas phenylalanine and valine have a higher preference for β-strand-like conformations. , …”

Section: Introductionmentioning

confidence: 99%

Ionized Trilysine: A Model System for Understanding the Nonrandom Structure of Poly-l-lysine and Lysine-Containing Motifs in Proteins

et al. 2012

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It is now well-established that different amino acid residues can exhibit different conformational distributions in the unfolded state of peptides and proteins. These conformational propensities can be modulated by nearest neighbors. In the current study, we combined vibrational and NMR spectroscopy to determine the conformational distributions of the central and C-terminal residues in trilysine peptides in aqueous solution. The study was motivated by earlier observations suggesting that interactions between ionized nearest neighbor residues can substantially change conformational propensities. We found that the central lysine residue predominantly adopts conformations that are located at the upper border of the upper left quadrant of the Ramachandran plot and the left border of the polyproline II region. We term this type of conformation deformed polyproline II (pPII(d)). The structures of less populated subensembles of trilysine resemble are comparable with structures at the i + 1 position of type I and type II β-turns. For the C-terminal residue, however, we obtained a mixture of polyproline II, β-strand, and right-handed helical conformations, which is typical for lysine residues in alanine- and glycine-based peptides. Our data thus indicate that the terminal lysines modify and restrict the conformational distribution of the central lysine residue. DFT calculations for ionized trilysine and lysyllysyllysylglycine in vacuo indicate that the pPII(d) is stabilized by a rather strong hydrogen bond between the NH3(+) group of the central lysine and the carbonyl group of the C-terminal peptide. This intramolecular hydrogen bonding induces optical activity in the C-terminal CO stretching vibration, which leads to an unusual and relatively intense positive Cotton band. Additionally, we analyzed the amide I' band profile of ionized triornithine in water. Ornithine is structurally similar to lysine in that its side chain is terminated with an amino group; however, the side chain of ornithine is shorter than lysine's side chain by one methylene group. We found that the conformational distribution of the central ornithine in this peptide must be very similar to that of the central lysine residue in trilysine. This suggests that the ionized ammonium group, which lysine and ornithine side chains have in common, is the main determinant of their conformational propensities at the central position in the respective tripeptides. The results of a DFT-based geometry optimization confirm this notion. In principle, our results suggest that lysine-rich segments in unfolded/disordered proteins and peptides can switch between different types of local order, i.e., an extended pPII(d)-like conformation and transient turns. However, for longer polylysine segments nonlocal interactions between side chains might impede the formation of turns, thus enabling the formation of pPII(d)-helix segments.

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“…Generally, amide I band profiles are used to determine the fraction of different secondary structures in a (folded) protein or peptide [5]. Over the past ten years, the excitonic coupling between amide I modes have been used for a more refined analysis of mostly unfolded short peptides [14,18,19]. With respect to β-sheets, theoretical and computational studies have focused on amide I in the respective IR and, to a more limited extent, in the VCD spectra [15,17,20].…”

Section: Introductionmentioning

confidence: 99%

Simulation of IR, Raman and VCD amide I band profiles of self-assembled peptides

Schweitzer‐Stenner

Measey

2010

Spectroscopy

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Vibrational spectroscopy is a suitable and convenient tool to probe the self-assembly of peptides, a biomedically and biotechnologically relevant process. Theoretical efforts to quantitatively analyze vibrational spectra of peptide aggregates have thus far focused on exploring the IR and to a lesser extent the vibrational circular dichroism (VCD) spectra of rather small sized planar or nearly planar β-sheet structure. The current study utilizes an algorithm based on an excitonic coupling model with experimentally or computationally determined parameters to simulate the amide I band profiles of the IR, isotropic Raman, anisotropic Raman and VCD spectra of two-and three-dimensional β-sheet structures. In agreement with earlier calculations we found that the splitting between the two prominent IR bands of an antiparallel β-sheet increases with increasing number of strands until a saturation is reached at approximately eight strands. The dominant isotropic and anisotropic Raman bands of amide I are located between the two IR bands and downshift only slightly with increasing sheet length. The VCD signal is rather weak. We also investigated the influence of sheet stacking on amide I by calculating the respective IR, Raman and VCD profiles for two in-register, facially stacked β-sheets with seven strands per sheet for an antiparallel arrangement of the sheets and six strands per sheet for a parallel arrangement. We found that stacking produces additional bands in the IR and Raman spectrum, in line with the reduced symmetry of the ideal unit cell of the β-sheet. In addition, a more pronounced VCD signal is detected. A comparison with experimental IR, Raman and VCD spectra of gelated (AAKA) 4 reveals a good qualitative agreement between experimental and simulated amide I band profiles.

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The Structure of Unfolded Peptides and Proteins Explored by Vibrational Spectroscopy

Cited by 10 publications

References 128 publications

Short peptides as predictors for the structure of polyarginine sequences in disordered proteins

Short peptides as predictors for the structure of polyarginine sequences in disordered proteins

Ionized Trilysine: A Model System for Understanding the Nonrandom Structure of Poly-l-lysine and Lysine-Containing Motifs in Proteins

Simulation of IR, Raman and VCD amide I band profiles of self-assembled peptides

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