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Faster magic-angle spinning leads to a resolution revolution in biological solid-state NMR

Objective

Solid-state NMR has recently made a significant impact on structural biology by providing atomic-resolution structures of several, previously uncharacterized proteins. A particularly relevant example is the Amyloid-beta (Aβ) peptide linked to Alzheimer’s disease where we determined the atomic-resolution structure of Aβ(1-42) and of the Osaka mutant of Aβ(1-40).
A spectral resolution revolution is now in reach that will enable solid-state NMR to address new frontiers in structural biology. The applications mentioned above are based on 13C-detected spectroscopy. Proton-detected experiments, although clearly more sensitive thanks to the high gyromagnetic ratio of 1H, have found few applications so far, due to the poor resolution of 1H spectra caused by the 1H-1H dipolar interaction. The proton resolution can be enhanced by employing faster rotation of the sample, i.e. higher MAS (magic-angle spinning) frequencies. Presently accessible MAS frequencies are already faster than the ones of any other man-made object. A significant improvement is still attainable in our view. Increasing the MAS frequency to 200-250 kHz will improve the spectral quality to favorably compare with solution NMR for larger proteins, including fully protonated systems. In addition, the amount of sample required is reduced by almost two orders of magnitude, to approx. 100 μg, compared to the about 10 mg needed in 13C-detected experiments. This removes an important bottleneck in sample-preparation. The resolution and sensitivity gain will allow the structural characterization of e.g. disease-relevant amyloids or membrane proteins with higher precision. Moreover, this approach will enable the investigation of complex systems, which presently elude structural characterization. The resolution revolution brought about by fast spinning shall thus represent a breakthrough since it will open new horizons for solving urgent biological and medical questions.

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Topic(s)

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ERC-ADG - Advanced Grant

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Call for proposal

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(opens in new window) ERC-2016-ADG

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Host institution

EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 2 173 375,00
Address
Raemistrasse 101
8092 Zuerich
Switzerland

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Region
Schweiz/Suisse/Svizzera Zürich Zürich
Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 2 173 375,00

Beneficiaries (1)

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