Unfolded peptides and proteins studied with infrared absorption and vibrational circular dichroism spectra

Keiderling, Timothy A.; Xu, Qi

doi:10.1016/s0065-3233(02)62007-8

Cited by 70 publications

(62 citation statements)

References 156 publications

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“…Beyond PPII being the dominant backbone conformation in peptides (4,(26)(27)(28)(29)(30)(31)(32)(33), Adzhubei and Sternberg found the presence of an average of over one stretch of four consecutive PPII residues in a library of 80 proteins (42). The origin of the preference for PPII in peptides may be due to preferential solvation (36)(37)(38), a suggestion that is consistent with the stretches of PPII tending to occur on the surfaces of these proteins.…”

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confidence: 74%

Helix, Sheet, and Polyproline II Frequencies and Strong Nearest Neighbor Effects in a Restricted Coil Library

et al. 2005

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A central issue in protein folding is the degree to which each residue's backbone conformational preferences stabilize the native state. We have studied the conformational preferences of each amino acid when the amino acid is not constrained to be in a regular secondary structure. In this large but highly restricted coil library, the backbone preferentially adopts dihedral angles consistent with the polyproline II conformation rather than R or conformations. The preference for the polyproline II conformation is independent of the degree of solvation. In conjunction with a new masking procedure, the frequencies in our coil library accurately recapitulate both helix and sheet frequencies for the amino acids in structured regions, as well as polyproline II propensities. Therefore, structural propensities for R-helices and -sheets and for polyproline II conformations in unfolded peptides can be rationalized solely by local effects. In addition, these propensities are often strongly affected by both the chemical nature and the conformation of neighboring residues, contrary to the Flory isolated residue hypothesis.

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confidence: 74%

Helix, Sheet, and Polyproline II Frequencies and Strong Nearest Neighbor Effects in a Restricted Coil Library

et al. 2005

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confidence: 84%

“…They concluded that charged polypeptides assume, at least locally, a rather ordered polyproline II (PPII) conformation, which is the structure adopted by trans-poly-L-proline. This notion was later confirmed by vibrational circular dichroism (VCD) studies on a variety of unfolded polypeptides and proteins (12,13).PPII is a rather regular structural motif in that it exhibits a perfect, left-handed threefold rotational symmetry (3 1 -helix) for its canonical conformation, with ( , ) ϭ (Ϫ78°, 146°) (14). Woody and coworkers (15-17) have published a series of papers proving that PPII gives rise to a far UV-ECD spectrum, which many in the scientific community still interpret as indicative of random coil (15).…”

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confidence: 91%

The alanine-rich XAO peptide adopts a heterogeneous population, including turn-like and polyproline II conformations

Schweitzer‐Stenner

Measey

2007

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

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The solution structure of the hepta-alanine polypeptide Ac-X 2A7O2-NH2 (XAO) has been a matter of controversy in the current literature. On one side of the argument is a claim that the peptide adopts a mostly polyproline II ( We have used an excitonic coupling model to simulate the amide I band of the FTIR, vibrational circular dichroism, and isotropic and anisotropic Raman spectra of XAO, where, for each residue, the backbone dihedral angle was constrained by using the reported 3 JC␣HNH values and a modified Karplus relation. The best reproduction of the experimental data could only be achieved by assuming an ensemble of conformations, which contains various ␤-turn conformations (Ϸ26%), in addition to ␤-strand (Ϸ23%) and PPII (Ϸ50%) conformations. PPII is the dominant conformation in segments not involved in turn formations. Most of the residues were found to sample the bridge region connecting the PPII and right-handed helix troughs in the Ramachandran plot, which is part of the very heterogeneous ensemble of conformations generally termed type IV ␤-turn.alanine propensity ͉ amide I ͉ unfolded peptides ͉ vibrational spectroscopy T he unfolded state of peptides and proteins has been the subject of an increasing number of experimental and theoretical studies (1-9), owing to the discovery of naturally disordered, although biologically functioning, proteins and peptides (9), and the general relevance for a thorough understanding of the protein folding process. In this context, the possible existence of local residue structure would certainly affect the initial phase of the folding process (10). The existence of such locally ordered segments has first been proposed by Tiffany and Krimm (11) based on electronic circular dichroism (ECD) measurements on poly-L-proline, poly-L-lysine, and poly-L-glutamic acid. They concluded that charged polypeptides assume, at least locally, a rather ordered polyproline II (PPII) conformation, which is the structure adopted by trans-poly-L-proline. This notion was later confirmed by vibrational circular dichroism (VCD) studies on a variety of unfolded polypeptides and proteins (12,13).PPII is a rather regular structural motif in that it exhibits a perfect, left-handed threefold rotational symmetry (3 1 -helix) for its canonical conformation, with ( , ) ϭ (Ϫ78°, 146°) (14). Woody and coworkers (15-17) have published a series of papers proving that PPII gives rise to a far UV-ECD spectrum, which many in the scientific community still interpret as indicative of random coil (15). Recently, they reported a very convincing quantitative agreement between the PPII content of ␤II proteins, derived from crystallographic data, and ECD spectra (16). The PPII signal was also observed in the spectrum of the unfolded state of many proteins subjected to denaturing detergents (17). Thermal denaturation, however, often yields a conformation that is reflected by a weak, nearly symmetric, couplet with a positive maximum between 180 and 210 nm and a negative minimum between 210 and 230 nm (11,16,18). ECD ...

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“…At 323 K there is much more disorder in the chain under conditions where sheet is preferred, and the conformational equilibrium is similar to the unfolded conformations in lysozyme (residues 39-100) and PrP (residues 110-142). This effect is not limited to polyLys; the importance of the P II conformation is becoming increasingly appreciated (57)(58)(59)(60)(61).…”

Section: Methodsmentioning

confidence: 99%

Pauling and Corey's α-pleated sheet structure may define the prefibrillar amyloidogenic intermediate in amyloid disease

Armen

DeMarco²,

Alonso³

et al. 2004

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

132

170

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Transthyretin, ␤2-microglobulin, lysozyme, and the prion protein are four of the best-characterized proteins implicated in amyloid disease. Upon partial acid denaturation, these proteins undergo conformational change into an amyloidogenic intermediate that can self-assemble into amyloid fibrils. Many experiments have shown that pH-mediated changes in structure are required for the formation of the amyloidogeneic intermediate, but it has proved impossible to characterize these conformational changes at high resolution using experimental means. To probe these conformational changes at atomic resolution, we have performed molecular dynamics simulations of these proteins at neutral and low pH. In low-pH simulations of all four proteins, we observe the formation of ␣-pleated sheet secondary structure, which was first proposed by L. Pauling and R. B. Corey [(1951) Proc. Natl. Acad. Sci. USA 37, 251-256]. In all ␤-sheet proteins, transthyretin and ␤2-microglobulin, ␣-pleated sheet structure formed over the strands that are highly protected in hydrogen-exchange experiments probing amyloidogenic conditions. In lysozyme and the prion protein, ␣-sheets formed in the specific regions of the protein implicated in the amyloidogenic conversion. We propose that the formation of ␣-pleated sheet structure may be a common conformational transition in amyloidosis.

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Unfolded peptides and proteins studied with infrared absorption and vibrational circular dichroism spectra

Cited by 70 publications

References 156 publications

Helix, Sheet, and Polyproline II Frequencies and Strong Nearest Neighbor Effects in a Restricted Coil Library

Helix, Sheet, and Polyproline II Frequencies and Strong Nearest Neighbor Effects in a Restricted Coil Library

The alanine-rich XAO peptide adopts a heterogeneous population, including turn-like and polyproline II conformations

Pauling and Corey's α-pleated sheet structure may define the prefibrillar amyloidogenic intermediate in amyloid disease

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