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Atomic Scale Structural Studies of Macromolecular Assemblies by Solid-state Nuclear Magnetic Resonance Spectroscopy
Published on: September 17, 2017
Absolute structural constraints on amyloid fibrils from solid-state NMR spectroscopy of partially oriented samples
1Laboratory of Chemical Physics, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Building 5, Room 112, Bethesda, Maryland 20892-0520, USA.
Journal of the American Chemical Society
|April 9, 2004
Summary
Solid-state NMR provides molecular-level structural insights into amyloid fibrils. This method determines fibril orientation by analyzing magic-angle spinning sideband patterns in 13C NMR spectra.
Area of Science:
- Biophysics
- Structural Biology
- Neuroscience
Background:
- Amyloid fibrils are associated with neurodegenerative diseases like Alzheimer's.
- Determining the precise molecular structure of amyloid fibrils is crucial for understanding disease mechanisms.
- Solid-state Nuclear Magnetic Resonance (NMR) is a powerful technique for studying protein structures.
Purpose of the Study:
- To demonstrate that absolute, molecular-level structural information can be obtained from solid-state NMR of partially oriented amyloid fibrils.
- To determine the orientation of the fibril axis relative to the carbonyl 13C chemical shift anisotropy (CSA) tensor.
- To validate structural models of amyloid fibrils.
Main Methods:
- Utilizing magic-angle spinning (MAS) sideband patterns in 13C NMR spectra.
- Analyzing fibrils deposited on planar substrates to create an anisotropic orientation distribution.
- Measuring the fibril axis direction relative to the carbonyl CSA tensor of Val12 in Abeta1-40 fibrils.
Main Results:
- Absolute structural information was obtained from solid-state NMR measurements.
- The direction of the fibril axis relative to the carbonyl 13C CSA tensor was determined.
- Experimental results for Abeta1-40 fibrils align with predictions from a parallel beta-sheet structural model.
Conclusions:
- Solid-state NMR on partially oriented amyloid fibrils yields absolute structural data.
- The method accurately determines fibril orientation relative to molecular tensors.
- This technique can be used to validate and refine structural models of amyloid fibrils.
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