Conformational distributions of denatured and unstructured proteins are similar to those of 20 × 20 blocked dipeptides

Jung, Young-Sang; Hwang, Gwi Seo; Cho, Minhaeng

doi:10.1007/s10858-012-9618-5

Cited by 22 publications

(36 citation statements)

References 69 publications

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“…Table and Figures S7 and S8 show that the δH N and δH α values of dipeptides are better correlated with those of the host–guest peptide models than chemical shift database models. This indicates that the conformational distributions and local environments of the host–guest peptide models are quite similar to those of the blocked dipeptides . However, it should be noted that, to obtain an improved set of reference values, the NMR experimental conditions, e.g., denaturant concentration, temperature, and pH, should be properly controlled to be the same with actual experimental conditions for target proteins.…”

Section: Resultsmentioning

confidence: 99%

Neighboring Residue Effects in Terminally Blocked Dipeptides: Implications for Residual Secondary Structures in Intrinsically Unfolded/Disordered Proteins

2014

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For nuclear magnetic resonance (NMR)-based protein structure determinations, the random coil chemical shifts are very important because the secondary and tertiary protein structure predictions become possible by examining deviations of measured chemical shifts from those reference chemical shift values. In addition, neighboring residue effects on chemical shifts and J-coupling constants are crucial in understanding the nature of conformational propensities exhibited by unfolded or intrinsically disordered proteins. We recently reported the 1D NMR results for a complete set of terminally blocked dipeptides (Oh KI, Jung YS, Hwang GS, Cho M. J Biomol NMR 2012;53:25-41), but the NMR resonance assignments were not possible so that the average chemical shifts and J-coupling constants were only considered. In the present work, to thoroughly investigate the neighboring residue effects and random coil chemical shifts we extend the previous studies with 2D NMR, and measured all the (3) J(HNHα) values and H(α) and H(N) chemical shifts of the same set of terminally blocked dipeptides that are free from structural effects like secondary structure, hydrogen-bond, long-range backbone, and side-chain interactions. In particular, the preceding and following residue effects on amino-acid backbone conformational propensities are revealed and directly compared with previous works on either short peptides or empirical chemical shift database.

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Section: Resultsmentioning

confidence: 99%

Neighboring Residue Effects in Terminally Blocked Dipeptides: Implications for Residual Secondary Structures in Intrinsically Unfolded/Disordered Proteins

2014

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“…13, 34, 35 Oh et al used NMR and CD spectroscopy to analyze the conformational properties of 361 blocked tripeptides. 44, 45 In contrast, other researchers used unblocked peptides like trialanine (AAA) and GxG (x: different guest amino acid residues) for conformational studies, in part because these types of peptides allow more comprehensive NMR studies and provide a better spectral resolution in the amide I window of vibrational spectra, which is a highly prominent tool for the structure analysis of peptides and proteins alike. 5-7, 10, 11, 46-50 The choice of unblocked tripeptides was justified with experimental evidence for the limited influence of terminal charges on the conformation of their central residues.…”

Section: Introductionmentioning

confidence: 99%

pH-Independence of Trialanine and the Effects of Termini Blocking in Short Peptides: A Combined Vibrational, NMR, UVCD, and Molecular Dynamics Study

et al. 2013

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Several lines of evidence now well establish that unfolded peptides in general, and alanine in specific, have an intrinsic preference for the polyproline II (pPII) conformation. Investigation of local order in the unfolded state is, however, complicated by experimental limitations and the inherent dynamics of the system, which has in some cases yielded inconsistent results from different types of experiments. One method of studying these systems is the use of short model peptides, and specifically short alanine peptides, known for predominantly sampling pPII structure in aqueous solution. Recently, He et al. (J. Am. Chem. Soc. 2012, 134, 1571–1576) proposed that unblocked tripeptides may not be suitable models for studying conformational propensities in unfolded peptides due to the presence of end effect, i.e. electrostatic interactions between investigated amino acid residues and terminal charges. To determine whether changing the protonation states of the N- and C-termini influence the conformational manifold of the central amino acid residue in tripeptides, we have examined the pH-dependence of unblocked trialanine and the conformational preferences of alanine in the alanine dipeptide. To this end, we measured and globally analyzed amide I’ band profiles and NMR J-coupling constants. We described conformational distributions as the superposition of two-dimensional Gaussian distributions assignable to specific sub-spaces of the Ramachandran plot. Results show that the conformational ensemble of trialanine as a whole, and the pPII content (χpPII=0.84) in particular, remain practically unaffected by changing the protonation state. We found that compared to trialanine, the alanine dipeptide has slightly lower pPII content (χpPII=0.74) and an ensemble more reminiscent of the unblocked Gly-Ala-Gly model peptide. In addition, a two-state thermodynamic analysis of the conformational sensitive Δε(T) and 3J(HNHα)(T) data obtained from electronic circular dichroism and H-NMR spectra indicate that the free energy landscape of trialanine is similar in all protonation states. MD simulations for the investigated peptides corroborate this notion and show further that the hydration shell around unblocked trialanine is unaffected by the protonation/deprotonation of the C-terminal group. In contrast, the alanine dipeptide shows a reduced water density around the central residue as well as a less ordered hydration shell, which decreases the pPII propensity and reduces the lifetime of sampled conformations.

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“…Oh et al . employed a similar approach to analyze the 3 J(H N H α ) coupling constants of blocked tripeptides 16, 17. Grdadolnik et al .…”

Section: Introductionmentioning

confidence: 99%

Disorder and order in unfolded and disordered peptides and proteins: A view derived from tripeptide conformational analysis. I. Tripeptides with long and predominantly hydrophobic side chains

Schweitzer‐Stenner¹,

Hagarman²,

Toal³

et al. 2013

Proteins

119

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We performed a conformational analysis of the central residues of three tripeptides glycyl-L-isoleucyl-glycine (GIG), glycyl-L-tyrosyl-glycine (GYG) and glycyl-L-arginyl-glycine (GRG) in aqueous solution, based on a global analysis of amide I' band profiles and NMR J-coupling constants. The results are compared with recently reported distributions of GVG, GFG and GEG. For GIG and GYG, we found that even though the polyproline II (pPII) fraction is below 0.5, it is still the most populated conformation, whereas GVG and GFG show both a larger β-strand fraction. For GRG, we observed a clear dominance of pPII over β-strand, reminiscent of observations for GEG and GKG. This finding indicates that terminal charges on otherwise hydrophobic residue side chains stabilize pPII over β-strand conformations. For all peptides investigated we found that a variety of compact and turn-like conformations constitute nearly 20 percent of their conformational distributions. Attempts to analyze our data with a simple two-state pPII-->/<--β model therefore do not yield any satisfactory reproduction of experimental results. A comparison of the obtained GxG ensembles with conformational distributions of GxG segments in truncated coil libraries (helices and sheets omitted) revealed a much larger fraction of type II β(i+2) and type III β like conformations for the latter. Thus, a comparison of conformational distributions of unfolded peptide segments in solution and in coil libraries reveal interesting information on how the interplay between intrinsic propensities of amino acid residues and non-local interactions in polypeptide chains determine the conformations of loop segments in proteins.

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Conformational distributions of denatured and unstructured proteins are similar to those of 20 × 20 blocked dipeptides

Cited by 22 publications

References 69 publications

Neighboring Residue Effects in Terminally Blocked Dipeptides: Implications for Residual Secondary Structures in Intrinsically Unfolded/Disordered Proteins

Neighboring Residue Effects in Terminally Blocked Dipeptides: Implications for Residual Secondary Structures in Intrinsically Unfolded/Disordered Proteins

pH-Independence of Trialanine and the Effects of Termini Blocking in Short Peptides: A Combined Vibrational, NMR, UVCD, and Molecular Dynamics Study

Disorder and order in unfolded and disordered peptides and proteins: A view derived from tripeptide conformational analysis. I. Tripeptides with long and predominantly hydrophobic side chains

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