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. Fields of science natural sciencesbiological sciencesbiochemistrybiomoleculesproteinssocial sciencespolitical sciencespolitical transitionsrevolutionsnatural sciencesbiological sciencesmolecular biologystructural biologynatural sciencesphysical sciencesopticsspectroscopy Keywords Solid-state nuclear magnetic resonance spectroscopy Programme(s) H2020-EU.1.1. - EXCELLENT SCIENCE - European Research Council (ERC) Main Programme Topic(s) ERC-2016-ADG - ERC Advanced Grant Call for proposal ERC-2016-ADG See other projects for this call Funding Scheme ERC-ADG - Advanced Grant Host institution EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH Net EU contribution € 2 173 375,00 Address Raemistrasse 101 8092 Zuerich Switzerland See on map Region Schweiz/Suisse/Svizzera Zürich Zürich Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 2 173 375,00 Beneficiaries (1) Sort alphabetically Sort by Net EU contribution Expand all Collapse all EIDGENOESSISCHE TECHNISCHE HOCHSCHULE ZUERICH Switzerland Net EU contribution € 2 173 375,00 Address Raemistrasse 101 8092 Zuerich See on map Region Schweiz/Suisse/Svizzera Zürich Zürich Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Total cost € 2 173 375,00
