Probing water accessibility in HET-s(218–289) amyloid fibrils by solid-state NMR

Van Melckebeke H, Schanda P, Gath J, Wasmer C, Verel R, Lange A, Meier BH, Böckmann A. 2011. Probing water accessibility in HET-s(218–289) amyloid fibrils by solid-state NMR. Journal of Molecular Biology. 405(3), 765–772.

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Journal Article | Published | English
Author
Van Melckebeke, Hélène; Schanda, PaulIST Austria ; Gath, Julia; Wasmer, Christian; Verel, René; Lange, Adam; Meier, Beat H.; Böckmann, Anja
Abstract
Despite the importance of protein fibrils in the context of conformational diseases, information on their structure is still sparse. Hydrogen/deuterium exchange measurements of backbone amide protons allow the identification hydrogen-bonding patterns and reveal pertinent information on the amyloid β-sheet architecture. However, they provide only little information on the identity of residues exposed to solvent or buried inside the fibril core. NMR spectroscopy is a potent method for identifying solvent-accessible residues in proteins via observation of polarization transfer between chemically exchanging side-chain protons and water protons. We show here that the combined use of highly deuterated samples and fast magic-angle spinning greatly attenuates unwanted spin diffusion and allows identification of polarization exchange with the solvent in a site-specific manner. We apply this measurement protocol to HET-s(218–289) prion fibrils under different conditions (including physiological pH, where protofibrils assemble together into thicker fibrils) and demonstrate that each protofibril of HET-s(218–289), is surrounded by water, thus excluding the existence of extended dry interfibril contacts. We also show that exchangeable side-chain protons inside the hydrophobic core of HET-s(218–289) do not exchange over time intervals of weeks to months. The experiments proposed in this study can provide insight into the detailed structural features of amyloid fibrils in general.
Publishing Year
Date Published
2011-01-21
Journal Title
Journal of Molecular Biology
Volume
405
Issue
3
Page
765-772
ISSN
IST-REx-ID

Cite this

Van Melckebeke H, Schanda P, Gath J, et al. Probing water accessibility in HET-s(218–289) amyloid fibrils by solid-state NMR. Journal of Molecular Biology. 2011;405(3):765-772. doi:10.1016/j.jmb.2010.11.004
Van Melckebeke, H., Schanda, P., Gath, J., Wasmer, C., Verel, R., Lange, A., … Böckmann, A. (2011). Probing water accessibility in HET-s(218–289) amyloid fibrils by solid-state NMR. Journal of Molecular Biology. Elsevier. https://doi.org/10.1016/j.jmb.2010.11.004
Van Melckebeke, Hélène, Paul Schanda, Julia Gath, Christian Wasmer, René Verel, Adam Lange, Beat H. Meier, and Anja Böckmann. “Probing Water Accessibility in HET-s(218–289) Amyloid Fibrils by Solid-State NMR.” Journal of Molecular Biology. Elsevier, 2011. https://doi.org/10.1016/j.jmb.2010.11.004.
H. Van Melckebeke et al., “Probing water accessibility in HET-s(218–289) amyloid fibrils by solid-state NMR,” Journal of Molecular Biology, vol. 405, no. 3. Elsevier, pp. 765–772, 2011.
Van Melckebeke H, Schanda P, Gath J, Wasmer C, Verel R, Lange A, Meier BH, Böckmann A. 2011. Probing water accessibility in HET-s(218–289) amyloid fibrils by solid-state NMR. Journal of Molecular Biology. 405(3), 765–772.
Van Melckebeke, Hélène, et al. “Probing Water Accessibility in HET-s(218–289) Amyloid Fibrils by Solid-State NMR.” Journal of Molecular Biology, vol. 405, no. 3, Elsevier, 2011, pp. 765–72, doi:10.1016/j.jmb.2010.11.004.

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