Direct Determination of a Peptide Torsional Angle ψ by Double-Quantum Solid-State NMR

Feng, Xiaolong; Edén, Mattias; Brinkmann, Andreas; Luthman, Henrik; Eriksson, Lars; Gräslund, Astrid; Antzutkin, Oleg N.; Levitt, Malcolm H.

doi:10.1021/ja972252e

Cited by 121 publications

(122 citation statements)

References 14 publications

(33 reference statements)

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“…Backbone torsion angles in TTR(105-115) fibrils (Table 1 and Table 3, which is published as supporting information on the PNAS web site) were determined by using 3D dipolar-chemical shift correlation experiments, which report on the relative orientations of 1 H-15 N, 1 H-13 C, and 13 C-15 N dipolar tensors (31)(32)(33)(34). It is well established that these experiments have regions of highest angular resolution and sensitivity for molecular conformations that correspond to relatively small deviations from the parallel or antiparallel orientation of the two dipole vectors of interest (i.e., projection angles of ͉⌰͉ Ϸ 0-30°).…”

Section: Resultsmentioning

confidence: 99%

“…For the peptide backbone, the experiment which correlates the 1 H N -15 N and 1 H ␣ -13 C ␣ dipolar coupling tensors within residue i, also referred to as 1 (31,32), is most sensitive for peptide conformations characterized by i Ϸ Ϫ120 Ϯ 30°(i.e., conformations in the ␤-sheet region of Ramachandran space). The torsion angle actually probed in the 1 (33,34) are particularly strongly dependent on those peptide conformations described by 90°Ͻ i Ͻ 150°and 150°Ͻ ͉ i ͉ Ͻ 180°, respectively (i.e., also in the ␤-sheet region of Ramachandran space). Thus, these experiments are exquisitely sensitive to the region of conformational space that is most relevant for the polypeptide chains within amyloid fibrils.…”

Section: Resultsmentioning

confidence: 99%

“…All torsion angle experiments used in the present work used two dimensions for frequency labeling with the isotropic chemical shifts and a third dipolar dephasing dimension, which encodes the torsion angle information by evolving correlated nuclear spin states under the relevant dipolar interactions (32). The theoretical background and spectral simulations for these torsion angle experiments have been described in detail (31)(32)(33)(34). Experimental and theoretical dipolar dephasing curves for the Tyr-105 and Thr-106 residues are shown in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…The NMR pulse sequences used for the measurement of the structural constraints have been described in detail (29)(30)(31)(32)(33)(34) and are not discussed extensively here. Briefly, the majority of 13 C-15 N distances were determined by using the 3D z-filtered transferred-echo double-resonance (3D ZF TEDOR) technique (30), and the backbone torsion angles were measured by using 3D dipolar-chemical shift correlation methods, 1 (33,34) for .…”

Section: Methodsmentioning

confidence: 99%

“…Briefly, the majority of 13 C-15 N distances were determined by using the 3D z-filtered transferred-echo double-resonance (3D ZF TEDOR) technique (30), and the backbone torsion angles were measured by using 3D dipolar-chemical shift correlation methods, 1 (33,34) for .…”

Section: Methodsmentioning

confidence: 99%

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High-resolution molecular structure of a peptide in an amyloid fibril determined by magic angle spinning NMR spectroscopy

Jaroniec

MacPhee

Bajaj

et al. 2004

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

483

464

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Amyloid fibrils are self-assembled filamentous structures associated with protein deposition conditions including Alzheimer's disease and the transmissible spongiform encephalopathies. Despite the immense medical importance of amyloid fibrils, no atomic-resolution structures are available for these materials, because the intact fibrils are insoluble and do not form diffraction-quality 3D crystals. Here we report the high-resolution structure of a peptide fragment of the amyloidogenic protein transthyretin, TTR(105-115), in its fibrillar form, determined by magic angle spinning NMR spectroscopy. The structure resolves not only the backbone fold but also the precise conformation of the side chains. Nearly complete 13 C and 15 N resonance assignments for TTR(105-115) formed the basis for the extraction of a set of distance and dihedral angle restraints. A total of 76 self-consistent experimental measurements, including 41 restraints on 19 backbone dihedral angles and 35 13 C-15 N distances between 3 and 6 Å were obtained from 2D and 3D NMR spectra recorded on three fibril samples uniformly 13 C, 15 N-labeled in consecutive stretches of four amino acids and used to calculate an ensemble of peptide structures. Our results indicate that TTR(105-115) adopts an extended ␤-strand conformation in the amyloid fibrils such that both the main-and side-chain torsion angles are close to their optimal values. Moreover, the structure of this peptide in the fibrillar form has a degree of long-range order that is generally associated only with crystalline materials. These findings provide an explanation of the unusual stability and characteristic properties of this form of polypeptide assembly.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

High-resolution molecular structure of a peptide in an amyloid fibril determined by magic angle spinning NMR spectroscopy

Jaroniec

MacPhee

Bajaj

et al. 2004

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

483

464

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Determination of the Amide-Plane Orientations in a Cyclo-β-Peptide by Magic-Angle-Spinning Deuterium-Correlation Spectroscopy, and Comparison with the Powder X-Ray Structure

Le¹,

Hintermann²,

Wessels³

et al. 2001

HCA

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Previously, it has been shown that the correlation of deuterium quadrupolar tensors by spin diffusion under slow magic-angle-spinning conditions can provide accurate measurements of their relative orientation. In the present work we apply the technique to the cyclo-with its amide hydrogens labeled by deuterons. From the 2D spin-diffusion spectrum, it is possible to determine the mutual orientation of the amide deuteron quadrupolar coupling tensors. Assuming that the molecule has four-fold molecular symmetry, the polar angles of the symmetry axis in the principal-axis frames of the deuterium electric-field-gradient tensors are found to be q 15.78 AE 1.08 or q 164.38 AE 1.08, and f AE 728 AE 108. They are used to deduce possible conformations of the peptide based on the result of a previous measurement that correlated the deuterium principal quadrupolar frame with a local molecular frame. We found eight conformations that are all consistent with the NMR measurement. Three of these have acceptably small van der Waals contact energies. One of the three structures agrees, within a rmsd of 68 for the backbone dihedral angles, with an X-ray conformation.

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Nuclear Magnetic Resonance of Biomolecules

Evans

2000

Encyclopedia of Analytical Chemistry

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Nuclear magnetic resonance (NMR) spectroscopy exploits a property of the nucleus known as nuclear spin, which exhibits angular momentum and as such generates a local magnetic field that can be influenced by a larger static external field. In the presence of a large external magnet, the nuclear spins align with the field, with a slight excess opposed to the field. That small excess can be flipped to alignment with the field in the presence of a radiofrequency (RF) pulse of appropriate frequency. Relaxation of those spins back to the ground state results in emission of RF radiation whose frequency is an indication of the local electron density of the molecule in which the spin resides. Such information can ultimately be directly related to molecular structure. NMR spectroscopy is unique in that it can be used to image the whole human body at one extreme, and determine the three‐dimensional (3D) structure of a biomolecule within the body at the other extreme. The principal advantages of NMR are that: (i) the complete molecular structure can be determined; (ii) the technique spans all principal states of matter (solid, liquid, gas); (iii) the method is nondestructive and can be used noninvasively, as in a clinical setting. The principal disadvantages of NMR are that: (i) the technique is very insensitive (typically samples below 50 µM are difficult to study, although recent advances in nanoprobe and cryprobe technology are rapidly revising these numbers); (ii) in liquids there are molecular weight limits of around 50 kDa – although there are new methods being developed that may have a significant impact on this; (iii) in solids only limited structural information can be obtained to date.

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Direct Determination of a Peptide Torsional Angle ψ by Double-Quantum Solid-State NMR

Cited by 121 publications

References 14 publications

High-resolution molecular structure of a peptide in an amyloid fibril determined by magic angle spinning NMR spectroscopy

High-resolution molecular structure of a peptide in an amyloid fibril determined by magic angle spinning NMR spectroscopy

Determination of the Amide-Plane Orientations in a Cyclo-β-Peptide by Magic-Angle-Spinning Deuterium-Correlation Spectroscopy, and Comparison with the Powder X-Ray Structure

Nuclear Magnetic Resonance of Biomolecules

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