Nitrogen-15 chemical shift tensors and conformation of solid polypeptides containing 15N-labeled L-alanine residue by 15N NMR. 2. Secondary structure is reflected in .sigma.22

Shoji, Akira; Ozaki, Takuo; Fujito, Teruaki; Deguchi, K.; Ando, Shinji; Ando, Isao

doi:10.1021/ja00168a011

Cited by 67 publications

(103 citation statements)

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“…R < 1/2, the transition temperatures between an α-helical state to a non-α-helical state are between T * =0.085 and T * =0.11. These results are qualitatively in good agreement with experiments which show that polyalanine adopts an α-helical conformation in hydrophobic environments such as the solid state or in non-polar organic solutions and a β-structure conformation in polar aqueous solution 88,[106][107][108][109][110][111] . This is similarly observed in experiments on many heterogeneous peptides which can be folded into alternative stable structures by changing the solution conditions such as the pH, salt or organic cosolvent concentration, peptide concentration, and the redox state [112][113][114][115][116][117][118][119][120][121][122][123][124][125][126] .…”

Section: Resultssupporting

confidence: 90%

Spontaneous Fibril Formation by Polyalanines; Discontinuous Molecular Dynamics Simulations

Nguyen

Hall

2006

J. Am. Chem. Soc.

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Fibrillary protein aggregates rich in β-sheet structure have been implicated in the pathology of several neurodegenerative diseases. In this work, we investigate the formation of fibrils by performing discontinuous molecular dynamics simulations on systems containing 12 to 96 model Ac-KA 14 K-NH 2 peptides using our newly-developed off-lattice, implicit-solvent, intermediateresolution model, PRIME. We find that at a low concentration, random-coil peptides assemble into α-helices at low temperatures. At intermediate concentrations, random-coil peptides assemble into α-helices at low temperatures and large β-sheet structures at high temperatures. At high concentrations, the system forms β-sheets over a wide range of temperatures. These assemble into fibrils above a critical temperature which decreases with concentration and exceeds the isolated peptide's folding temperature. At very high temperatures and all concentrations, the system is in a random-coil state. All of these results are in good qualitative agreement with those by Blondelle and coworkers on Ac-KA 14 K-NH 2 peptides. The fibrils observed in our simulations mimic the structural characteristics observed in experiments in terms of the number of sheets formed, the values of the intra-and inter-sheet separations, and the parallel peptide arrangement within each β-sheet. Finally, we find that when the strength of the hydrophobic interaction between non-polar sidechains is high compared to the strength of hydrogen bonding, amorphous aggregates, rather than fibrillar aggregates, are formed.

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Section: Resultssupporting

confidence: 90%

Spontaneous Fibril Formation by Polyalanines; Discontinuous Molecular Dynamics Simulations

Nguyen

Hall

2006

J. Am. Chem. Soc.

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“…Accordingly, polyalanine is expected to adopt an ␣-helical conformation in a nonpolar organic solvent and ␤-structures with coil conformations in a polar aqueous solution. Solid-state (i.e., hydrophobic environment) (42)(43)(44)(45) and aqueous solution (12)(13)(14) measurements of polyalanine support its conformational dependence on the chemical environments with the ubiquity of the ␣-helix and ␤-structures prevailing in hydrophobic and in polar environments, respectively. The dependence of the conformation of alanine on the solvent characteristics (i.e., the polarity and dielectric constant of the solvent) is supported by experimental evidence that the helical propensity of alanine in water shows a dramatic increase on addition of certain alcohols (e.g., trifluoroethanol) (46,47).…”

Section: Resultsmentioning

confidence: 87%

Solvent effects on the energy landscapes and folding kinetics of polyalanine

Levy

Jortner

Becker

2001

Proc. Natl. Acad. Sci. U.S.A.

146

132

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The effect of a solvation on the thermodynamics and kinetics of polyalanine (Ala12) is explored on the basis of its energy landscapes in vacuum and in an aqueous solution. Both energy landscapes are characterized by two basins, one associated with ␣-helical structures and the other with coil and ␤-structures of the peptide. In both environments, the basin that corresponds to the ␣-helical structure is considerably narrower than the basin corresponding to the ␤-state, reflecting their different contributions to the entropy of the peptide. In vacuum, the ␣-helical state of Ala12 constitutes the native state, in agreement with common helical propensity scales, whereas in the aqueous medium, the ␣-helical state is destabilized, and the ␤-state becomes the native state. Thus solvation has a dramatic effect on the energy landscape of this peptide, resulting in an inverted stability of the two states. Different folding and unfolding time scales for Ala12 in hydrophilic and hydrophobic chemical environments are caused by the higher entropy of the native state in water relative to vacuum. The concept of a helical propensity has to be extended to incorporate environmental solvent effects.T he chemical environment exerts a fundamental influence on the structure, thermodynamics, and dynamics of polypeptides. Particularly, the solvent may affect the dynamics and structure of the polypeptide and consequently alter its function, as has been demonstrated in a variety of biologically important phenomena, ranging from the rate of oxygen uptake in myoglobin to the stabilization of opposite-charged side-chain pairs at the surface of proteins (1, 2). The variance of the properties of a polypeptide in different solvents depends on the nature of the solvent-polypeptide intermolecular interactions, which lead to a rich repertoire of phenomena. These interactions involve the effect of organic solvents on the destabilization of the hydrophobic core and the exposure of side chains, as well as the opposite effects of aqueous solvents on the protein structures favoring the hydrophilic protein surface and the hydrophobic core (1, 3). Theoretical and computational evidence (4-6) for medium effects on polypeptide structures has accumulated. Following the Zimm-Bragg theory of the helix-coil equilibrium (7), it has been established that short polypeptides should not form helices in water. Indeed, numerous studies report that the relative tendency for helix formation in water is low at physiological temperatures (6,8).The structure of polyalanine peptides is of considerable interest as, in general, regardless of specific chemical environments, the commonly reported secondary structure propensity scales for amino acids (9-11) rank alanine as having the highest ␣-helical propensity. However, experimental (12-14) and computational (4-6, 15-23) studies showed that polyalanines tend to adopt random-coil conformations in aqueous solution. The ambiguity of the helical propensities, even for alanine, which is known as an excellent helix former, may indic...

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“…Spectra were obtained from averaging at least 4000 transients. The "N chemical shifts are given relative to the lSN chemical shift of NH,' (11.59 ppm from the 15N chemical shift of Gly in the solid state) [30].…”

Section: Methodsmentioning

confidence: 99%

A High‐resolution ¹⁵N Solid‐state NMR Study of Collagen and Related Polypeptides

Naito¹,

Tuzi²,

Saitô³

1994

European Journal of Biochemistry

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High-resolution solid-state 15N-NMR was used to clarify the effect of hydration on the stability of the coiled-coil triple-helix conformation of Gly-X,,-Y,, repeating units in collagen and the collagen-like polypeptides, (Pro-Ala-Gly), and (Pro-Pro-Gly),,, because the stability is thought to be related to the presence of (Gly)NH...O=C(X,, or Pro) hydrogen bonds. The 15N-NMR signals of these samples were narrowed upon hydration, mainly due to hydration-induced conformational change or rearrangement of the repeating units. In particular, the I5N chemical shifts of the Gly N-H group and the high-field (low-frequency) shoulder peak of Pro nitrogen signals in (Pro-Pro-Gly),, were shifted downfield (4.9 ppm and 6.8 ppm, respectively) with increasing relative humidity, while the corresponding peaks for collagen and (Pro-Ala-Gly), were unchanged and close to the 15N shift of (Pro-Pro-Gly),, in the hydrated state. Such downfield shifts are consistent with the formation of N-H-O=C hydrogen bonds. In agreement with the NMR results, it was found that the (Gly)NH-.O=C (Xaa or Pro) hydrogen bonds are retained in dehydrated collagen fibrils but not in partially dehydrated (Pro-Pro-Gly),,,. No evidence was obtained for the partial formation of the 3, helix form (Pro), or (Gly), either under hydrated or dehydrated conditions. It is concluded that the Gly 15N chemical shift is a very sensitive probe for studying supercoiling in collagen and collagenlike polypeptides.Collagen is the major structural protein of connective tissues and bones. Its secondary structure has been determined from fiber X-ray diffraction as a coiled-coil triple helix consisting of a repeating Gly-X,,-Y,, (triplet) sequence in which positions X , and Y,, are frequently occupied by Pro and Hyp (hydroxy-L-prolyl) residues, respectively [l -31. Such a triple helix (collagen-I1 form) could be stabilized by the only interchain hydrogen bonds formed between Gly N-H and the carbonyl group of the amino acid residues in the X,,positions and the amide group of Gly residues positioned internally at each turn of the helix. It has been pointed out that hydration further stabilizes the collagen structure [4, 51. In fact, the Xray diffraction pattern becomes reversibly disordered upon dehydration [6]. Furthermore, it was demonstrated that strong interactions exist between collagen and water molecules, as manifested in the splitting of the deuterium quadrupole by 'H-NMR of D,O adsorbed on collagen fiber [7], infrared dichroism measurements [8] and the identification of three or four strongly bound water molecules/triplet by X-ray diffraction [9]. The additional stabilization of the triple helix could be achieved by formation of a water bridge [hydrogen bond through water molecule(s)] between the hydroxy group of Correspondence to H. Sait6, Department of Life Science, Himeji Institute of Technology, Harima Science Garden City, Kamigori, Hyogo, Japan 678-12Abbreviations. CP-MAS, cross-polarization magic-angle spinning ; T, , , cross-polarization time; TYo, proton-spin-lattice...

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Nitrogen-15 chemical shift tensors and conformation of solid polypeptides containing 15N-labeled L-alanine residue by 15N NMR. 2. Secondary structure is reflected in .sigma.22

Cited by 67 publications

References 2 publications

Spontaneous Fibril Formation by Polyalanines; Discontinuous Molecular Dynamics Simulations

Spontaneous Fibril Formation by Polyalanines; Discontinuous Molecular Dynamics Simulations

Solvent effects on the energy landscapes and folding kinetics of polyalanine

A High‐resolution ¹⁵N Solid‐state NMR Study of Collagen and Related Polypeptides

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Nitrogen-15 chemical shift tensors and conformation of solid polypeptides containing 15N-labeled L-alanine residue by 15N NMR. 2. Secondary structure is reflected in .sigma.22

Cited by 67 publications

References 2 publications

Spontaneous Fibril Formation by Polyalanines; Discontinuous Molecular Dynamics Simulations

Spontaneous Fibril Formation by Polyalanines; Discontinuous Molecular Dynamics Simulations

Solvent effects on the energy landscapes and folding kinetics of polyalanine

A High‐resolution 15N Solid‐state NMR Study of Collagen and Related Polypeptides

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A High‐resolution ¹⁵N Solid‐state NMR Study of Collagen and Related Polypeptides